nanoparticle drug delivery

Cowpea Mosaic Virus Delivers Drugs to Kill Cancer Cells

2010-03-10T09:05:00.001-08:00

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Norwich BioScience Institutes have developed particles from the Cowpea mosaic virus can carry anti-cancer agents to cancer cells.

Materials View China - Cowpea Mosaic Virus Unmodified Empty Viruslike Particles Loaded with Metal and Metal Oxide

Empty (devoid of RNA) viruslike particles (eVLPs) of Cowpea mosaic virus can now be obtained readily. CPMV can encapsulate, within the protein capsid, cobalt or iron oxide by environmentally benign processes. The external surface also remains amenable to chemical modification. The development of eVLPs for targeted delivery of therapeutic agents is now a reality.

7 pagse of supplemental material

In 2008, there was the first work on using the tobacco mosaic virus to deliver siRNA to cells

Tobacco mosaic virus is like a 18-nanometer wide straw, which can hold gene silencing RNA.

“The speed with which you develop siRNA drugs is truly amazing,” said Stephen Hyde. “In the past, a traditional small molecule drug might take several years of intensive research effort by a large team of scientists to develop. Today, with siRNA technology, it is possible for a single researcher to develop a drug candidate in a few weeks.”

Block copolymer nanotemplating of tobacco mosaic and tobacco necrosis viruses (Nov 2008)

Joural of Virology -Interaction of the Tobacco Mosaic Virus Replicase Protein with a NAC Domain Transcription Factor Is Associated with the Suppression of Systemic Host Defenses (Oct 2009)

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Buckywire for drug delivery and more

2009-06-17T09:13:00.000-07:00

Synthesis of a fullerene-based one-dimensional nanopolymer
through topochemical transformation of the parent nanowire (30 page pdf)

Large-scale practical applications of fullerene (C60) in nanodevices could be significantly facilitated if the commercially-available micrometer-scale raw C60 powder were further processed into a one-dimensional (1D) nanowire-related polymer displaying covalent bonding as molecular interlinks and resembling traditional important conjugated polymers. However, there has been little study thus far in this area despite the abundant literature on fullerene. Here we report the synthesis and characterization of such a C60-based nanowire polymer, (-C60TMB-)n, where TMB=1,2,4-trimethylbenzene, which displays a well-defined crystalline structure, exceptionally large length-to-width ratio and excellent thermal stability. The material is prepared by first growing the corresponding nanowire through a solution phase of C60 followed by a topochemical polymerization reaction in the solid state. Gas chromatography, mass spectrometry and 13C nuclear magnetic resonance evidence is provided for the nature of the covalent bonding mode adopted by the polymeric chains. Theoretical analysis based on detailed calculations of the reaction energetics and structural analysis provides an in-depth understanding of the polymerization pathway. The nanopolymer promises important applications in biological fields and in the development of optical, electrical, and magnetic nanodevices.

From MIT Technology Review Blog:

The exciting thing about this breakthrough is the potential to grow buckywires on an industrial scale from buckyballs dissolved in a vat of bubbling oil. Since the buckywires are insoluble, they precipitate out, forming crystals. (Here it ought to be said that various other groups are said to have made buckywires of one kind or another, but none seem to have nailed it from an industrial perspective.)

So what might buckywires be good for? First up is photovoltaics: these buckywires look as if they could be hugely efficient light harvesters because of their great surface area and the way that they can conduct photon-liberated electrons. Then there are various electronic applications in wiring up molecular circuit boards.

But perhaps the area of greatest interest is drug delivery. Geng and co suggest that buckywires ought to be safer than carbon nanotubes because the production method is entirely metal-free.

We have demonstrated for the first time an approach to the synthesis of a C60-based nanowire polymer and established the chemical bonding mode involved in the polymeric chains based on both experimental measurements and theoretical calculations. Importantly, the material adopts a crystalline 1D nanostructure which resembles carbon nanotubes in shape and other important conjugated polymers in structure. Since the material does not contain any metal but is simply composed almost entirely of carbon (while it contains hydrogen, the content is only 1.4 wt %), it suggests biological compatibility and it is, perhaps, even more attractive than carbon nanotubes for bio-applications. In addition, the material has further important potential for applications in photo-electrical devices because of the intrinsically large magnitude of the nonlinear optical response of C60 and the excellence of its photoinduced charge transfer properties. Considering all these, we believe that this work represents a step toward true applications of C60 in nanotechnology by the ability of processing commercially available raw C60 powder into a one-dimensional, crystalline, and covalently-bonded fullerene nanopolymer.

We consider that applications of the reported nanopolymer may be facilitated by a wet chemical approach through surface modification of the material using the rich chemistry of fullerene developed over the last 20 years. Since the nanopolymer is insoluble in common solvents, such surface modification or functionalization should be possible to achieve in either an aqueous or an organic solution without destructing its solid-state structure. Such a wet approach would benefit from low-cost processing, the need for only simple apparatus and the possibility of scaling-up to the industrial level. Moreover, the nanopolymer itself not only provides an example of phase transition of the parent nanowire driven by forming and breaking covalent bonds, but also illustrates the enduring significance of the original fullerene concept and its versatility as applied to new fullerene-related nanostructures. Finally, the host (C60) and guest (1,2,4-TMB) nature of the polymerization suggests a general host-guest route to the synthesis of new types of fullerene-based nanopolymers constructed by different organic monomers and fullerenes

Improved personalized cancer treatment with new RNAi delivery

2009-05-17T07:58:00.000-07:00

In technology that promises to one day allow drug delivery to be tailored to an individual patient and a particular cancer tumor, researchers at the University of California, San Diego School of Medicine, have developed an efficient system for delivering siRNA into primary cells. The work will be published in the May 17 in the advance on-line edition of Nature Biotechnology.

The team solved the problem of delivery of siRNAs into cells by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA's negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.

The researchers have a startup, Traversa Therapeutics, which is commercializing this work.

Traversa's siRNA delivery technology is specifically designed to avoid the physical size and bioavailability problems inherent in the Liposome/cationic-lipid approach. The technology is non-cytotoxic, delivers to the entire cell population and all cell-types tested, and is dramatically smaller than a liposome. The Company expects the technology to provide improved pharmacokinetics, distribution and bioavailability over other methods. The technology supports delivery to primary and tumor cells, T cells, B cells, Macrophage, neuronal cells and human stem cells, where other approaches have failed. This ability to induce RNA interference in entire cell populations and all cell types in a non-cytotoxic fashion is unique to Traversa's technology and provides the Company's competitive advantage.

Traversa's siRNA delivery technology (PTD-DRBD) is a protein comprised of multiple Peptide Transduction Domains (PTD) linked to a Double-stranded RNA Binding Domain (DRBD). The PTD portion of the protein induces delivery into the cell through a fluid-uptake mechanism that all cells perform, called macropinocytosis. The DRBD portion of the protein initially binds to the siRNA, and later releases the siRNA once inside the cell.

RNA Interference (RNAi) is a recently discovered natural biological process. The Central Dogma of biology is that DNA makes RNA, and RNA subsequently makes protein. Because undesired proteins are the cause of most human disease, pharmaceutical drugs typically target select proteins and block their function. RNAi works upstream from the manufacture of protein in cells, silencing genes and thereby blocking the creation of these disease-causing proteins before they are made.

This breakthrough discovery is being harnessed by RNAi researchers to develop an entirely new class of human therapeutic that could potentially treat sixty percent of all human disease – the Interfering RNA. This new class of drugs brings with it enormous potential:

- Significantly improved specificity of target molecules
- Greater efficacy with fewer side effects
- New drugs for rare or difficult to treat diseases
- Reduced drug discovery timelines
- Faster response to pandemic infection

Interfering RNAs have tremendous selectivity, degrade only target RNAs, and yield specific gene silencing. However, due to their relatively large size (~14,000-18,000 Daltons), they require an additional delivery technology in order to enter cells and produce their intended effect.

"RNAi has an unbelievable potential to manage cancer and treat it," said Steven Dowdy, PhD, Howard Hughes Medical Institute Investigator and professor of cellular and molecular medicine at UC San Diego School of Medicine. "While there's still a long way to go, we have successfully developed a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells."

For many years, Dowdy has studied the cancer therapy potential of RNA inhibition which can be used to silence genes through short interfering, double-stranded RNA fragments called siRNAs. But delivery of siRNAs has proven difficult due to their size and negative electrical charge – which prohibits them from readily entering cells.

A small section of protein called a peptide transduction domain (PTD) has the ability to permeate cell membranes. Dowdy and colleagues saw the potential for PTDs as a delivery mechanism for getting siRNAs into cancer cells. He and his team had previously generated more than 50 "fusion proteins" using PTDs linked to tumor-suppressor proteins.

"Simply adding the siRNAs to a PTD didn't work, because siRNAs are highly negatively charged, while PTDs are positively charged, which results in aggregation with no cellular delivery," Dowdy explained. The team solved the problem by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA's negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.

To determine the ability of this PTD-DRBD fusion protein to deliver siRNA, the researchers generated a human lung cancer reporter cell line. Using green and fluorescent protein and analyzing the cells using flow cytometry analysis, they were able to determine the magnitude of RNA inhibitory response and the percentage of cells undergoing this response. They found that the entire cellular population underwent a maximum RNAi response. Similar results were obtained in primary cells and cancer cell lines.

"We were subsequently able to introduce gene silencing proteins into a large percentage of various cell types, including T cells, endothelial cells and human embryonic stem cells," said Dowdy. "Importantly, we observed no toxicity to the cells or innate immune responses, and a minimal number of transcriptional off-target changes."

These RNAi methods can be continually tweaked to combat new mutations – a way to overcome a major problem associated with current cancer therapies. "Such therapies can't be used a second time if a cancer tumor returns, because the tumor has mutated the target gene to avoid the drug binding," said Dowdy. "But since the synthetic siRNA is designed to bind to a single mutation and only that mutation on the genome, it can be easily and rapidly changed while maintaining the delivery system – the PTD-DRBD fusion protein."

"Cancer is a complex, genetic disease that is different in every patient," Dowdy added. "This is still in early stages, but I believe the siRNA-induced RNAi approach to personalized cancer treatment is the only thing on the table."

DNA Boxes Could Deliver Drugs

2009-05-06T23:25:00.000-07:00

Chemistry World is reporting that Danish researchers have made a nano-sized box out of DNA that can be locked or opened in response to 'keys' made from short strands of DNA. By changing the nature or number of these keys, it should be possible to use the boxes as sensors, drug delivery systems or even molecular computers.

To make the box shape, the team took a long, circular single strand of DNA from a virus that infects bacteria called bacteriophage M13. This M13 sequence is a cheap source of single-stranded DNA and is convenient size for building with. To turn this ring of DNA into a box, the team used a computer to work out exactly the right combination of short strands of complementary DNA which could 'staple' the appropriate areas of the ring together to get the desired box shape. When they mixed the M13 strand with the 220 short 'staple strands' and heated them up for an hour, the boxes neatly self-assembled.

Kjems reveals that the group have already had some success with putting cargo inside the boxes, including enzymes and quantum dots. 'It's quite big (about 30nm) inside - it could fit virus particles or quite big enzymes and other macromolecules.' In terms of applications, Kjems can foresee three main purposes for the box: 'One is as a calculator or logic gate; the second is for controlled release, for example of drugs, in response to external stimuli; and the last is as a sensor - where the thing you are sensing causes the box to open or close and give a readout.'

The DNA origami technique is quite straightforward, Mao comments, so could be applied to all sorts of similar structures. The fact that the box can be easily opened and closed also makes it ideal for moving guest molecules around. 'I'm really looking forward to seeing what the group do next,' he adds.

MIT Technology Review also has coverage.

Deoxyribose sugar cubes: Because complementary regions of DNA like to pair up, researchers were able to design a long strand of DNA that, combined with many tiny DNA staples, would automatically assemble itself into a nano-sized box. This technique is known as DNA origami. Here, the boxes were imaged using cryo-electron tomography to confirm their cubelike structures and hollow interior.
Credit: : Ebbe S. Andersen, Aarhus University

21 pages of supplemental information from the Journal Nature article.

The abstract in the journal Nature. [Nature 459, 73-76 (7 May 2009) | doi:10.1038/nature07971; Received 9 November 2008; Accepted 6 March 2009]
Self-assembly of a nanoscale DNA box with a controllable lid

The unique structural motifs and self-recognition properties of DNA can be exploited to generate self-assembling DNA nanostructures of specific shapes using a 'bottom-up' approach1. Several assembly strategies have been developed for building complex three-dimensional (3D) DNA nanostructures. Recently, the DNA 'origami' method was used to build two-dimensional addressable DNA structures of arbitrary shape that can be used as platforms to arrange nanomaterials with high precision and specificity. A long-term goal of this field has been to construct fully addressable 3D DNA nanostructures. Here we extend the DNA origami method into three dimensions by creating an addressable DNA box 42 36 36 nm3 in size that can be opened in the presence of externally supplied DNA 'keys'. We thoroughly characterize the structure of this DNA box using cryogenic transmission electron microscopy, small-angle X-ray scattering and atomic force microscopy, and use fluorescence resonance energy transfer to optically monitor the opening of the lid. Controlled access to the interior compartment of this DNA nanocontainer could yield several interesting applications, for example as a logic sensor for multiple-sequence signals or for the controlled release of nanocargos.

FURTHER INVESTIGATION

The DNA origami design software program with documentation and tutorials is
available here: http://www.cdna.dk/origami/.

Nanodiamond drug device could transform cancer treatment

2008-10-03T10:13:00.000-07:00

Nanodiamond-embedded devices could be used to deliver a broad range of therapeutics for the treatment of cancer and inflammation and for regenerative medicine. The extremely thin and flexible devices also can be customized to any shape and thickness.

A Northwestern University research team has developed a promising nanomaterial-based biomedical device that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been surgically removed.

The flexible microfilm device, which resembles a piece of plastic wrap and can be customized easily into different shapes, has the potential to transform conventional treatment strategies and reduce patients' unnecessary exposure to toxic drugs. The device takes advantage of nanodiamonds, an emergent technology, for sustained drug release.

In their study, Ho and his colleagues embedded millions of tiny drug-carrying nanodiamonds in the FDA-approved polymer parylene. Currently used as a coating for implants, the biostable parylene is a flexible and versatile material resembling plastic wrap. A substantial amount of drug can be loaded onto clusters of nanodiamonds, which have a high surface area. The nanodiamonds then are put between extremely thin films of parylene, resulting in a device that is minimally invasive.

To test the device's drug release performance, the researchers used Doxorubicin, a chemotherapeutic used to treat many types of cancer. They found the drug slowly and consistently released from the embedded nanodiamond clusters for one month, with more Doxorubicin in reserve, indicating a more prolonged release (several months and longer) was possible. The device also avoided the "burst" or massive initial release of the drug, a common disadvantage with conventional therapy.

In control experiments, where the drug was present but without the nanodiamonds, virtually all of the drug was released within one day. By adding the drug-laden nanodiamonds to the device, drug release was instantly lengthened to the months-long timescale.

In addition to their large surface area, nanodiamonds have many other advantages that can be utilized in drug delivery. They can be functionalized with nearly any type of therapeutic. They can be suspended easily in water, which is important for biomedical applications. The nanodiamonds, each being four to six nanometers in diameter, are minimally invasive to cells, biocompatible and do not cause inflammation, a serious complication. And they are very scalable and can be produced in large quantities.

The architecture of the device is amenable to housing small molecule, protein, antibody or RNA- or DNA-based therapeutics. This gives the technology the potential to impact a range of treatment strategies where implanted, long-term drug release is needed.

A complex hybrid Nanoparticle slightly smaller than a virus deliver drug cocktail

2008-09-12T11:23:00.000-07:00

The nanometer-sized cargo ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. Credit: Ji-Ho Park, UCSD

Scientists at UC San Diego, UC Santa Barbara and MIT report that their nano-cargo-ship system integrates therapeutic and diagnostic functions into a single device that avoids rapid removal by the body’s natural immune system. It is 50 nanometers in size. So it has three times less volume than the typical virus.


1 nm    diameter of glucose molecule 
2 nm    diameter of DNA helix 
5 nm    diameter of insulin molecule 
6 nm    diameter of a hemoglobin molecule 
10 nm   thickness of cell wall (gram negative bacteria) 
75 nm   size of typical virus 
200 nm  diameter of smallest bacteria 
1000nm  diameter of sperm cell (smallest cell in the human body)

“The idea involves encapsulating imaging agents and drugs into a protective ‘mother ship’ that evades the natural processes that normally would remove these payloads if they were unprotected,” said Michael Sailor, a professor of chemistry and biochemistry at UCSD who headed the team of chemists, biologists and engineers that turned the fanciful concept into reality. “These mother ships are only 50 nanometers in diameter, or 1,000 times smaller than the diameter of a human hair, and are equipped with an array of molecules on their surfaces that enable them to find and penetrate tumor cells in the body.”

These microscopic cargo ships could one day provide the means to more effectively deliver toxic anti-cancer drugs to tumors in high concentrations without negatively impacting other parts of the body.

The researchers designed the hull of the ships to evade detection by constructing them of specially modified lipids--a primary component of the surface of natural cells. The lipids were modified in such a way as to enable them to circulate in the bloodstream for many hours before being eliminated. This was demonstrated by the researchers in a series of experiments with mice.

The researchers loaded their ships with three payloads before injecting them in the mice. Two types of nanoparticles, superparamagnetic iron oxide and fluorescent quantum dots, were placed in the ship’s cargo hold, along with the anti-cancer drug doxorubicin. The iron oxide nanoparticles allow the ships to show up in a Magnetic Resonance Imaging, or MRI, scan, while the quantum dots can be seen with another type of imaging tool, a fluorescence scanner.

This study provides the first example of a single nanomaterial used for simultaneous drug delivery and multimode imaging of diseased tissue in a live animal," said Ji-Ho Park, a graduate student in Sailor's laboratory who was part of the team. Geoffrey von Maltzahn, a graduate student working in Bhatia's laboratory, was also involved in the project, which was financed by a grant from the National Cancer Institute of the National Institutes of Health.

The nano mother ships look individually like a chocolate-covered nut cluster, in which a biocompatible lipid forms the chocolate shell and magnetic nanoparticles, quantum dots and the drug doxorubicin are the nuts. They sail through the bloodstream in groups that, under the electron microscope, look like small, broken strands of pearls.

The researchers are now working on developing ways to chemically treat the exteriors of the nano ships with specific chemical "zip codes," that will allow them to be delivered to specific tumors, organs and other sites in the body.

Tobacco Mosaic Virus can deliver gene silencing RNA and enables new drugs in weeks

2008-09-04T11:03:00.000-07:00

Tobacco mosaic virus is like a 18-nanometer wide straw, which can hold gene silencing RNA

The tobacco mosaic virus appears to be the key to safe and effective delivery of gene silencing RNA.

Bentley's team has successfully hollowed out the virus and filled it with siRNA, and then used it to slip the frail substance into all sorts of cells, from kidney tissue to cancer. The researchers have proven that the tiny capsules provide adequate protection, and that they release their payloads once inside -- hitting their target genes right on the mark.

The short, double-stranded RNA molecules known as siRNA can program cells to destroy disease-causing proteins. Their molecules turn on a cell's own built-in disease-fighting mechanisms. They can be programmed for a wide range of ailments -- from cancers to viruses -- and because they use the cell's own defense mechanisms, they produce minimal side effects.

In addition to treating cancers and genetic disorders, siRNA could prove useful against a variety of rare diseases that have, and always will be, overlooked by big pharmaceutical companies -- the long tail of disease.

People suffering from similar, exotic maladies could band together and recruit a small team of scientists, as if they were the Seven Samurai, to champion their cause and quickly design a cure.

“The speed with which you develop siRNA drugs is truly amazing,” said Stephen Hyde. “In the past, a traditional small molecule drug might take several years of intensive research effort by a large team of scientists to develop. Today, with siRNA technology, it is possible for a single researcher to develop a drug candidate in a few weeks.”

Bentley is optimistic that the virus will not cause health problems because most people already have traces of it in their blood -- from second-hand smoke -- and it does not seem to cause irritation or obvious immune-system problems.

Protecting the payload is not the only challenge, said Ben Berkhout, a biotechnology expert at the University of Amsterdam. Even if the delicate molecules are packaged in the perfect substance, they still need some sort of a guidance system.

"You want to efficiently get the siRNA drug into the cells where the therapeutic action should be,” said Berkhout.

By coating each tube with special proteins that can recognize and penetrate cancer cells, Bentley's team hopes to make smart drugs that will only go where they are needed.

If that trick works, tobacco may finally be able to turn over a new leaf.

Carbon nanotubes could reduce side effects from cancer treatment.

2008-08-29T11:24:00.001-07:00

MIT Technology Review reports that carbon nanotubes could reduce the side effects of cancer drugs and mice tests show they are twice as effective at reducing tumor size. The researchers estimate that drug uptake within a tumor was 10 times higher for nanotube delivery than for Taxol. This uptake means that smaller doses could be used to achieve the same effects as other treatments, reducing side effects.

Research from Stanford University has shown that carbon nanotubes loaded with anticancer drugs can target tumor cells while steering clear of healthy tissue.

The nanotubes--on average 100 nanometers long and a few nanometers wide--pass easily through the leaky walls of tumor blood vessels but do not get into healthy blood vessels. So the researchers realized that drugs attached to the nanotubes could be carried inside tumors without harming normal tissue.

To make working nano-drug transporters, the researchers coated the nanotubes with a molecule called polyethylene glycol (PEG), which has three branches on one end, then attached molecules of the anticancer drug paclitaxel to each branch. Each of the 100-nanometer-long nanotubes carried about 150 drug molecules in total. "Think of a carbon nanotube as a boat," says Steve Lippard, a chemistry professor at MIT, who was not involved in the research. "The advantage of the branched PEG is that you can have multiple passengers at each seat." Dai adds that the branched PEG is stable in the bloodstream for a relatively long time, giving the nanotubes more time to find and treat a tumor before leaving the body.

The drug-delivery technique was tested in mice that had been injected with breast cancer cells. Once the tumors grew to a specific size, the researchers administered a dose of the drug-laden nanotubes every six days. They gave another group of mice similar doses of different forms of paclitaxel, including the clinical drug Taxol, and left some untreated. After 22 days, they found that the tumors treated by nanotube delivery were less than half the size of the tumors treated by the second most effective treatment, Taxol.

Nanobialys can carry drugs to tumors or plaques

2008-07-30T15:33:00.000-07:00

Ultra-miniature bialy-shaped particles — called nanobialys because they resemble tiny versions of the flat, onion-topped rolls popular in New York City — could soon be carrying medicinal compounds through patients' bloodstreams to tumors or atherosclerotic plaques.

The nanobialys answered a need for an alternative to the research group's gadolinium-containing nanoparticles, which were created for their high visibility in magnetic resonance imaging (MRI) scans.

Gadolinium is a common contrast agent for MRI scans, but recent studies have shown that it can be harmful to some patients with severe kidney disease.

"The nanobialys contain manganese instead of gadolinium," says first author Dipanjan Pan, Ph.D., research instructor in medicine in the Cardiovascular Division. "Manganese is an element found naturally in the body. In addition, the manganese in the nanobialys is tied up so it stays with the particles, making them very safe."

A bialy is a Polish roll like a bagel without a hole that can be made with different toppings.

Nanoworms (magnetic iron oxide particles with polymer coating) target cancer tumors

2008-05-07T19:17:00.000-07:00

Segmented "nanoworms" composed of magnetic iron oxide and coated with a polymer are able to find and attach to tumors. Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors. They are superparamagnetic and show up very well on MRIs and can circulate in the body for hours since they do not trigger the immune system.

Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.

“Most nanoparticles are recognized by the body's protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”

The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.

“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”

The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.

“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”

Folded up micrometer-scale 'voxels' for drug delivery

2008-04-29T13:01:00.000-07:00

After starting the folds using magnetic forces, the structure is sealed using capillary action.

USC researchers have made pyramid structures that are 40 micrometers on each side

Part one is the creation of flat patterns, origami, of exactly the fold up shapes familiar to kindergarten children making paper pyramids, cubes or other solids, except that these are as small 40 micrometers (µm) on a side. (1 inch = 25,400 µm)

Instead of paper, the USC researchers created the patterns in polysilicon sitting on top of a thin film of gold, using a well-established commercial silicon wafer process called PolyMUMPs. The next step was clearing the polysilicon off the hinge areas by etching.

When the blanks were later electrocoated with permalloy to make them magnetic, the photomask used left hinge areas uncoated, to make sure they were the places that folded.

Then the folding had to be accomplished. First the researchers bent the hinges by application of magnetic force to the permalloy. Water pressure and capillary forces generated by submerging the tiny blanks in water, and drying them off did the final folding into shape.

The experiments spend considerable time comparing various methods of controlling the closure effects of water drying with simple flaps designed to close over each other to form "envelops," the directing water from different directions sequence the closing. Varying the time of trying could produce tighter seams.

Nanodiamonds 100 times cheaper, used to track cells in the body and deliver chemotherapy drugs

2008-04-29T12:54:00.000-07:00

Taiwanese scientists have found a way to slash the cost of making the diamond chips by around 100 times.

Nanodiamond's fluorescent properties could be used to track cells moving through the body. And, last year, researchers showed they could safely deliver chemotherapy drugs.

Cheaper alternatives to nanodiamonds, such as fluorescent dyes or small chunks of semiconductor known as quantum dots, are in use already. The diamonds, though, are less prone to blinking on and off than fluorescent dyes, and are not toxic to cells, unlike quantum dots.

FNDs are usually made by firing a high-energy electron beam into commercially available diamond powder and heating it up to 800 °C. Huan-Cheng Chang and colleagues at Academia Sinica in Taipei shoot a much less intense, and hence cheaper, beam of helium ions at diamond powder to make FNDs of the same quality.

Chang's team could track the movement of a single fluorescent nanodiamond within a cell for over 3 minutes.

The researchers have also explored other applications for their cheap diamonds, such as using them to monitor stem cells in developing tissue, or to carry drugs into cells.

"In particular, we have demonstrated that FNDs are able to interact with plasmid DNA and to deliver different genes into cultured human cells," Chang told New Scientist. That could be used for gene therapy, or DNA vaccines.

Chang and his colleagues have set up a commercial operation selling their nanodiamonds and are working on making them even smaller and to fluoresce more brightly.

The cheaper diamond chips need to be made smaller, though, if they are to perform well as markers to reveal the inner workings of cells, he adds.

Tiny Magnets for more effective Gene Therapy targeting for cancer, arthritis, heart disease and more

2008-04-18T17:08:00.000-07:00

The technique involves inserting nanomagnets into monocytes - a type of white blood cell used to carry gene therapy - and injecting the cells into the bloodstream. The researchers then placed a small magnet over the tumour to create a magnetic field and found that this attracted many more monocytes into the tumour.

This new technique could also be used to help deliver therapeutic genes in other diseases like arthritic joints or ischemic heart tissue.

Though the concept of magnetic targeting for drug and gene delivery has been around for decades, major technical hurdles have prevented its translation into a clinical therapy. By harnessing and enhancing the monocytes' innate targeting abilities, this technique offers great potential to overcome some of these barriers and bring the technology closer to the clinic.

The team are now looking at how effective magnetic targeting is at delivering a variety of different cancer-fighting genes, including ones which could stop the spread of tumours to other parts of the body.

Nanoparticle enabled cooking of cancer tumors moving to clinical trials in about three year

2008-04-13T16:16:00.000-07:00

Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with harmless radio waves could be in clinical trials as early as 3 years. The treatment has been 100% effective in animal trials.

Stanford uses gold nanoparticles, carbon nanotubes and lasers to image to the nanometer in the body

2008-03-31T20:22:00.000-07:00

Stanford University School of Medicine researchers has developed a new type of imaging system that can illuminate tumors in living subjects—getting pictures with a precision of nearly on nanometer (one-trillionth of a meter).

This technique, called Raman spectroscopy, expands the available toolbox for the field of molecular imaging, said team leader Sanjiv Sam Gambhir, MD, PhD, professor of radiology. signals from Raman spectroscopy are stronger and longer-lived than other available methods, and the type of particles used in this method can transmit information about multiple types of molecular targets simultaneously.

“Usually we can measure one or two things at a time,” he said. “With this, we can now likely see 10, 20, 30 things at once.”

Gambhir said he believes this is the first time Raman spectroscopy has been used to image deep within the body, using tiny nanoparticles injected into the body to serve as beacons.

When laser light is beamed from a source outside the body, these specialized particles emit signals that can be measured and converted into a visible indicator of their location in the body.

Imaging of animals and humans can be done using a few different methods, including PET, magnetic resonance imaging, computed tomography, optical bioluminescence and fluorescence and ultrasound. However, said Gambhir, none of these methods so far can fulfill all the desired qualities of an imaging tool, which include being able to finely detect small biochemical details, being able to detect more than one target at a time and being cheap and easy to use.

Postdoctoral scholars Shay Keren, PhD, and Cristina Zavaleta, PhD, co-first authors of the study, found a way to make Raman spectroscopy a medical tool. To get there, they used two types of engineered Raman nanoparticles: gold nanoparticles and single-wall carbon nanotubes.

First, they injected mice with the some of the nanoparticles. To see the nanoparticles, they used a special microscope that the group had adapted to view anesthetized mice exposed to laser light. The researchers could see that the nanoparticles migrated to the liver, where they were processed for excretion.

Using a microscope they modified to detect Raman nanoparticles, the team was able to see targets on a scale 1,000 times smaller than what is now obtainable by the most precise fluorescence imaging using quantum dots.

When adapted for human use, they said, the technique has the potential to be useful during surgery, for example, in the removal of cancerous tissue. The extreme sensitivity of the imager could enable detection of even the most minute malignant tissues.

Nested' nanoparticles increase efficiency of drug delivery

2008-03-27T21:21:00.000-07:00

University of Texas researchers believe that by encasing their drugs in a series of nanoparticles they can produce a highly targeted treatment that bypasses the body's immune defences which have typically plagued other nanotechnology therapies.

These defences protect the body from foreign bodies that enter the bloodstream, including therapeutic nanoparticles. The different levels of attack include enzymes in the blood corrode the particles and microphage cells that actively attack and destroy the particles and remove them from the bloodstream.

These defences are so effective that on average just one out of every 100,000 drug molecules actually end up in the area they were meant to be targeting. In the past it had been difficult to find particles that could both penetrate these "biobarriers" and effectively find and target the correct tumour cells.

Mauro Ferrari's multistage delivery system overcomes these defences using a series of nanoparticles, contained one inside the other. As it passes through each barrier the drug sheds a shell to reveal a new particle that is best suited to the next line of immune defence

1. First the largest nanoparticle is a mesoporous silicon particle, designed to avoid attack by the microphages and which can withstand enzyme corrosion.

2. Once in their desired position, the silicon particles can release quantum dots or carbon nanotubes - both of which act as contrast agents for imaging applications. The carbon nanotubes can also be stimulated to produce heat, which itself could be used as a therapy.

These particles can also be used to deliver other therapeutic agents, to achieve high concentrations within the tumour without needing to increase the actual dosage of the drug. Ferrari is currently investigating the possibility of using the particles to deliver short interfering RNA (siRNA) molecules that could silence messenger RNA within a tumour cell to stop it reproducing.

FURTHER READING
Abstract of the paper : Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications

Lipid Polymer Nanocontainers with controlled permeability

2008-03-21T16:33:00.000-07:00

From Nano Letters, "Biofunctionalized Lipid−Polymer Hybrid Nanocontainers with Controlled Permeability"

We have successfully developed, for the first time, a novel polymer–lipid hybrid nanocontainer with controlled permeability functionality. The nanocontainer is made by nanofabricating holes with desired dimensions in an impermeable polymer scaffold by focused ion beam drilling and sealing them with lipid bilayers containing remote-controlled pore-forming channel proteins. This system allows exchange of solutions only after channel activation at will to form temporary pores in the container. Potential applications are foreseen in bionanosensors, nanoreactors, nanomedicine, and triggered delivery.

FURTHER READING
Alma Dudia's PhD thesis "Nanofabricated biohybrid structures for controlled drug delivery"

Nanoparticle synthesis techniques could grow functional devices out of solution

2008-03-21T14:50:00.000-07:00

Nanowerk reports on an important research direction in nanoparticle synthesis is the expansion from single-component nanoparticles to hybrid nanostructures that possess two or more functional properties thanks to the integration of different materials.

In their research, Zeng and Sun have been trying to find a cost-effective approach to hierarchically assemble nanoscale building blocks for functional materials and devices. "In the past, this has been largely done by complicated microfabrication techniques involving multi-step lithography" explains Zeng. "The core of our work is the development of a general route for synthesizing multi-component, hybrid nanostructures where different nanoscale building blocks are directly grown onto one another to realize materials with multifunctionality. We envision that one day scientists will be able to grow completely functional sensors or even computer chips out of the solution phase. Our work is one small step towards realizing this goal."

Using their general synthesis approach, the two groups have produced a rather comprehensive list of hybrid materials that can be grouped into four classes: magnetic-metallic, magnetic-semiconductor, semiconductor-metallic, and magnetic-metallic-semiconductor.

The range of applications for these multicomponent nanoparticles is wide. For instance, they can be used as multi-modal bio-markers combining the functionalities of imaging, guided drug delivery and hyperthermia. Integrating different material properties at the nanoscale may also provide new opportunities for discovering enhanced or entirely novel material properties. Zeng uses the example of a ferroelectric-ferromagnetic multicomponent structure that could be used for electric field control of magnetism. "Such new functionality may one day allow new device concepts in nanoelectronics" he says.

Three sets of challenges before we can see large-scale practical applications:
1) gaining a fundamental understanding of the chemistry and materials science issues involved, so that hybrid structures can be designed with a high degree of control;

2) gaining a fundamental understanding of the interactions at the nanoscale between different components, so that the novel physical properties that may originate from such coupling can be predicted and exploited; and

3) finally, the controlled assembly of such hybrid nanoscale building blocks into bulk materials

Novozymes and Upperton Collaborate on New Nanoparticle Drug Delivery

2008-03-21T14:47:00.000-07:00

Nanowerk reports that Novozymes announced a new collaboration agreement with Upperton Limited, a UK based Biotech Company specialising in novel nanoparticle-based drug delivery systems.

The two companies and will focus on the commercial exploitation of the jointly-owned rP-nano™ technology: a highly targeted drug delivery system which utilises the natural binding properties of recombinant protein nanoparticles to enhance drug and gene bioavailability.

They generate nanoparticles from recombinant proteins in a yeast-based expression system. rP-nano™ technology can generate precisely-sized nanoparticles within the range of 10nm to 120nm and can be optimised for Enhanced Permeability and Retention effect. The nanoparticles produced through this process retain the natural binding properties of the recombinant proteins from which they are made, and bind to specific cell types to enable more targeted drug delivery and improved bioavailability.

Nanoemulsion vaccines

2008-02-27T16:58:00.000-08:00

A novel technique for vaccinating against a variety of infectious diseases – using an oil-based emulsion placed in the nose, rather than needles – has proved able to produce a strong immune response against smallpox and HIV in two new studies.

The results build on previous success in animal studies with a nasal nanoemulsion vaccine for influenza, reported by University of Michigan researchers in 2003.

Nanoemulsion vaccines developed at the Michigan Nanotechnology Institute for Medicine and the Biological Sciences at U-M are based on a mixture of soybean oil, alcohol, water and detergents emulsified into ultra-small particles smaller than 400 nanometers wide, or 1/200th the width of a human hair. These are combined with part or all of the disease-causing microbe to trigger the body’s immune response.

The surface tension of the nanoparticles disrupts membranes and destroys microbes but does not harm most human cells due to their location within body tissues. Nanoemulsion vaccines are highly effective at penetrating the mucous membranes in the nose and initiating strong and protective types of immune response, Baker says. U-M researchers are also exploring nasal nanoemulsion vaccines to protect against bioterrorism agents and hepatitis B.

The smallpox results, which appear in the February issue of Clinical Vaccine Immunology, could lead to an effective human vaccine against smallpox that is safer than the present live-vaccinia virus vaccine because it would use nanoemulsion-killed vaccinia virus, says Baker.

Anna U. Bielinska, Ph.D., a research assistant professor in internal medicine at the U-M Medical School, and others on Baker’s research team developed a killed-vaccinia virus nanoemulsion vaccine which they placed in the noses of mice to trigger an immune response. They found the vaccine produced both mucosal and antibody immunity, as well as Th1 cellular immunity, an important measure of protective immunity.

When the mice were exposed to live vaccinia virus to test the vaccine’s protective effect, all of them survived, while none of the unvaccinated control mice did. The researchers conclude that the nanoemulsion vaccinia vaccine offers protection equal to that of the existing vaccine, without the risk of using a live virus or the need for an inflammatory adjuvant such as alum hydroxide.

In antibody immunity, antibodies bind invading microbes as they circulate through the body. In cellular immunity, the immune system attacks invaders inside infected cells. There is growing interest in vaccines that induce mucosal immunity, in which the immune system stops and kills the invader in mucous membranes before it enters body systems.

A National Institutes of Health program, the Great Lakes Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases, funded the research. If the federal government conducts further studies and finds the nanoemulsion smallpox vaccine effective in people, it could be a safer way to protect citizens and health care workers in the event of a bioterrorism attack involving smallpox, Baker says.

That would allay concerns about the current vaccine’s safety which arose in 2002. On the eve of the Iraq War, the Bush administration proposed a voluntary program to vaccinate military personnel and 500,000 health care workers with the existing vaccine to prepare for the possible use of smallpox virus as a biological weapon.

Silica nanoparticles more effectively deliver bacteria killing nitric oxide

2008-02-27T16:44:00.000-08:00

Mark Schoenfisch and his lab of analytical chemists at UNC have created nano-scale scaffolds made of silica and loaded with nitric oxide (NO) which can be released in a precisely controlled way. Nitric Oxide can be used to kill bacteria.

Schoenfisch, Hetrick and their colleagues tested their silica scaffolds head-to-head with small molecules against the bacteria Pseudomonas aeruginosa, which is commonly found in burn and other wound infections.

NO delivered by both methods completely killed the bacteria. But the silica nanoparticles delivered the NO right to the bacteria’s doorstep. In contrast, the small molecules released NO indiscriminately, and the concentration of NO is lost as it makes its way toward bacterial cells.

“With the silica particles, more NO actually reached the inside of the cells, enhancing the efficacy of the nanoparticles compared to the small molecule. So, the overall amount of NO needed to kill bacteria is much less with silica nanoparticles,” Schoenfisch said. “And, with small molecules, you’re left with potentially toxic byproducts,” Schoenfisch said. Using mouse cells, they proved that the silica nanoparticles weren’t toxic to healthy cells, but the small molecules were.

Future research will include studying additional bacterial strains, active targeting, preferential uptake and biodistribution studies.

Nanomaterials used to localize and control drug delivery

2008-01-22T17:05:00.000-08:00

Nanoscale polymer films, about four nanometers per layer, were used to build a sort of matrix or platform to hold and slowly release an anti-inflammatory drug. The films are orders of magnitude thinner than conventional drug deliver coatings, said Genhong Cheng, a researcher at UCLA’s Jonsson Comprehensive Cancer Center and one of the study’s authors. A nanometer is one billionth of a meter.

“Using this system, drugs could be released slowly and under control for weeks or longer,” said Cheng, a professor of microbiology, immunology and molecular genetics. “A drug that is given orally or through the bloodstream travels throughout the system and dissipates from the body much more quickly. Using a more localized and controlled approach could limit side effects, particularly with chemotherapy drugs.”

Researchers coated tiny chips with layers of the nanoscale polymer films, which are inert and helped provide a Harry Potter-like invisibility cloak for the chips, hiding them from the body’s natural defenses. They then added Dexamethasone, an anti-inflammatory drug, between the layers. The chips were implanted in mice, and researchers found that the Dexamethasone-coated films suppressed the expression of cytokines, proteins released by the cells of the immune system to initiate a response to a foreign invader. Mice without implants and those with uncoated implants were studied to compare immune response.

The uncoated implants generated an inflammatory response from the surrounding tissue, which ultimately would have led to the body’s rejection of the implant and the breakdown of its functionality. However, tissue from the mice without implants and the mice with the nano-cloaked implants were virtually identical, proving that the film-coated implants were effectively shielded from the body’s defense system, said Edward Chow, a former UCLA graduate student who participated in the study and is one of its authors.

The nanomaterial technology serves as a non-invasive and biocompatible platform for the delivery of a broad range of therapeutics, said Dean Ho, an assistant professor of biomedical and mechanical engineering with the McCormick School of Engineering and Applied Science, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the study’s senior author.

The technology also may prove to be an effective approach for delivering multiple drugs, controlling the sequence of multi-drug delivery strategies and enhancing the life spans of commonly implanted devises such as cardiac stents, pacemakers and continuous glucose monitors

Magnetic Nanoparticles could be used to control uptake of drugs by cell receptors

2008-01-18T10:40:00.000-08:00

For the first time, researchers have demonstrated a means of controlling cell functions with a physical, rather than chemical, signal. Immune cells coated with nanoparticles take up calcium in the presence of a magnetic field. Each nanoparticle measures approximately 30 nanometers in diameter.

In this image, yellow cells are taking up calcium in response to a localized magnetic field. Cells that are farther away from the field are shown in purple and do not take up calcium. Credit: Donald Ingber, Harvard Medical School

Using a magnetic field to pull together tiny beads targeted to particular cell receptors, Harvard researchers made cells take up calcium, and then stop, then take it up again.

This is another important step to cellular and molecular control to enable nanomedicine

Ingber's group demonstrated its method for biomagnetic control using a type of immune-system cell that mediates allergic reactions.

Targeted nanoparticles with iron oxide cores were used to mimic antigens in vitro. Each is attached to a molecule that in turn can attach to a single receptor on an immune cell. When Ingber exposes cells bound with these particles to a weak magnetic field, the nanoparticles become magnetic and draw together, pulling the attached cell receptors into clusters. This causes the cells to take in calcium. (In the body, this would initiate a chain of events that leads the cells to release histamine.) When the magnetic field is turned off, the particles are no longer attracted to each other, the receptors move apart, and the influx of calcium stops.

"It's not the chemistry; it's the proximity" that activates such receptors, says Ingber.

The approach could have a far-reaching impact, as many important cell receptors are activated in a similar way and might be controlled using Ingber's method.

"In recent years, there has been a realization that physical events, not just chemical events, are important" to cell function, says Shu Chien, a bioengineer at the University of California, San Diego. Researchers have probed the effects of physical forces on cells by, for example, squishing them between plates or pulling probes across their surfaces. But none of these techniques work at as fine a level of control as Ingber's magnetic beads, which act on single biomolecules.

Many drugs, from anticancer antibodies to hormones, work by activating cell receptors. Once a hormone is in the blood, however, there's no turning it on or off. "This shows that you can turn on and off the signal, and that you can do it instantly," says Christopher Chen, a bioengineer at the University of Pennsylvania. "That's something that's hard to do, for example, with an antibody."

Ingber has many ideas for devices that might integrate his method of cellular control. Magnetic pacemakers could use cells instead of electrodes to send electrical pulses to the heart. Implantable drug factories might contain many groups of cells, each of which makes a different drug when activated by a magnetic signal. Biomagnetic control might lead to computers that can take advantage of cells' processing power. "Cells do complex things like image processing so much better than computers," says Ingber. Ingber, who began the project in response to a call by the Defense Advanced Research Projects Agency for new cell-machine interfaces, acknowledges that his work is in its early stages. In fifty years, however, he expects that there will be devices that "seamlessly interface between living cells and machines."

FURTHER READING
Harvard Institute for Biologically Inspired Engineering.

Nanorobot drug delivery

2007-12-10T07:15:00.001-08:00

Adriano Cavalcanti is CEO and chairman of CAN Center for Automation in Nanobiotech. Adriano and his coleagues have proposed a nanorobot platform should enable patient pervasive monitoring, and details are given in prognosis with nanorobots application for intracranial treatments. This integrated system also points towards precise diagnosis and smart drug delivery for cancer therapy.

nanorobot for nanomedicine drug delivery

Simulated nanorobot for drug delivery

Fully operational nanorobots for biomedical instrumentation should be achieved as a result of nanobioelectronics and proteomics integration. The proposed platform should enable patient pervasive monitoring, and details are given in prognosis with nanorobots application for intracranial treatments. This integrated system also points towards precise diagnosis and smart drug delivery for cancer therapy.

The methodologies and the implemented 3D simulation described in our study served as a test bed for molecular machine prototyping. The numerical analysis and advanced simulations provided a better understanding on how nanorobots should interact inside the human body. Hence, based on such information, we have proposed the innovative hardware architecture with a nanorobot model for use in common medical applications. The nanorobot takes chemical and thermal gradient changes as interaction choices for in vivo treatments. The use of mobile phones with RF is adopted in this platform as the most effective approach for control upload, helping to interface nanorobots communication and energy supply.

The next steps in our work can be defined as follows: (a) model manufacturing with CNT-CMOS biochip integration; (b) laboratory studies for in vivo tests; and (c) commercialization. The pipeline for development in the medical sector typically requires research and efforts to get new ideas out of laboratories and into the marketplace

FURTHER READING
Nanorobot design website

They have written many papers on this work. Robert Freitas is involved in some of them.

Nanorobot architecture for medical target identification.

The nanorobot interaction with the described workspace shows how time actuation is improved based on sensor capabilities. Therefore, our work addresses the control and the architecture design for developing practical molecular machines. Advances in nanotechnology are enabling manufacturing nanosensors and actuators through nanobioelectronics and biologically inspired devices. Analysis of integrated system modeling is one important aspect for supporting nanotechnology in the fast development towards one of the most challenging new fields of science: molecular machines. The use of 3D simulation can provide interactive tools for addressing nanorobot choices on sensing, hardware architecture design, manufacturing approaches, and control methodology investigation.

Earlier work was with CMOS versions of small robots

Hardware architecture for nanorobots

Freitas' nanomedicine site

Center for Automation in Nanobiotech website

Remote-control nanoparticles deliver drugs directly into tumors

2007-11-24T16:01:00.000-08:00

MIT scientists have devised remotely controlled nanoparticles that, when pulsed with an electromagnetic field, release drugs to attack tumors.

Here, dark gray nanoparticles carry different drug payloads (one red, one green). A remotely generated five-minute pulse of a low-energy electromagnetic field releases the green drug but not the red. A five-minute pulse of a higher-energy electromagnetic field releases the red drug, which had been tethered using a DNA strand twice as long as the green tether, as measured in base pairs. Image courtesy / Bhatia/von Maltzahn, MIT. Derfus, UCSD

Toward cancer drugs that penetrate 10 times deeper into the brain

2007-11-12T11:09:00.000-08:00

A new drug-delivery system for cancer of the brain — one of the most difficult cancers to treat — has the potential to carry anticancer drugs 10 times deeper into tumors than conventional medications, researchers in Connecticut and New York report.

In the new study, Mark Saltzman and colleagues showed that linking the anticancer drug campothecin (CPT) to the polymer polyethylene glycol (PEG), increased drug diffusion to more than a centimeter from the implant site.

They also identified a promising CPT-PET compound that could deliver 11 times more medication to the tumor than the plain drug alone. For patients, those advantages could substantially improve chances for successful treatment, the researchers indicate.

Laser activate Gold nanorods trigger complex biochemical mechanism to kill cancer

2007-10-16T21:56:00.000-07:00

Researchers have shown how tiny "nanorods" of gold can be triggered by a laser beam to blast holes in the membranes of tumor cells, setting in motion a complex biochemical mechanism that leads to a tumor cell's self-destruction.

The gold rods are less than 15 nanometers wide and 50 nanometers long, or roughly 200 times smaller than a red blood cell. Their small size is critical for the technology's potential medical applications: the human immune system quickly clears away particles larger than 100 nanometers, whereas smaller nanoparticles can remain in the bloodstream far longer.

Shining light on the gold nanorods causes them to become extremely hot, ionizing the molecules around them.

"This generates a plasma bubble that lasts for about a microsecond, in a process known as cavitation," Wei said. "Every cavitation event is like a tiny bomb. Then suddenly, you have a gaping hole where the nanorod was."

The gold nanorods also are ideal for a type of optical imaging known as two-photon luminescence, used by Cheng and his research group to monitor the position of nanorods in real time during tumor-cell targeting. The imaging technique provides higher contrast and brighter images than conventional fluorescent imaging methods.

The findings suggest an optimal window of opportunity for applying near-infrared light to the nanorods for cancer treatment.

"We like to believe this opens the possibility of using nanorods for biomedical imaging as well as for therapeutic purposes," Cheng said.

The Purdue researchers observed that light-absorbing nanorods cause the formation of membrane "blebs, " similar to severe blistering. These blisters, however, are not produced directly by the high heat generated by the nanorods.

"The blebbing is triggered by the nanorods, but it's really caused through a complex biochemical pathway - a chemically induced process," Cheng said. "Extra calcium gets into the cell and triggers enzyme activity, which causes the infrastructure inside the cell to become loose, and that gives rise to the membrane blebs."

Researchers used a calcium-sensitive fluorescent dye to back up their argument that calcium influx caused the tumor cell death. When the nanorod-bearing tumor cells were maintained in a calcium-free nutrient medium, no blisters were formed if the nanorods were exposed to near-infrared light. But when the researchers added calcium to the medium, the blebbing took place immediately.

Although the technique offers promise for a new cancer treatment, it is too early to determine when it could be in clinical use, said Wei, who is collaborating with the National Cancer Institute to determine the suitability of the functionalized gold nanorods for future clinical studies.

Nanodiamonds delivery chemotherapy drugs without negative side effects

2007-10-12T14:06:00.000-07:00

Northwestern University researchers have shown that nanodiamonds -- much like the carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale -- are very effective at delivering chemotherapy drugs to cells without the negative effects associated with current drug delivery agents.

Their study, published online by the journal Nano Letters, is the first to demonstrate the use of nanodiamonds, a new class of nanomaterials, in biomedicine. In addition to delivering cancer drugs, the model could be used for other applications, such as fighting tuberculosis or viral infections, say the researchers.

Nanodiamonds promise to play a significant role in improving cancer treatment by limiting uncontrolled exposure of toxic drugs to the body. The research team reports that aggregated clusters of nanodiamonds were shown to be ideal for carrying a chemotherapy drug and shielding it from normal cells so as not to kill them, releasing the drug slowly only after it reached its cellular target.

To make the material effective, Ho and his colleagues manipulated single nanodiamonds, each only two nanometers in diameter, to form aggregated clusters of nanodiamonds, ranging from 50 to 100 nanometers in diameter. The drug, loaded onto the surface of the individual diamonds, is not active when the nanodiamonds are aggregated; it only becomes active when the cluster reaches its target, breaks apart and slowly releases the drug. (With a diameter of two to eight nanometers, hundreds of thousands of diamonds could fit onto the head of a pin.)

“The nanodiamond cluster provides a powerful release in a localized place -- an effective but less toxic delivery method,” said co-author Eric Pierstorff, a molecular biologist and post-doctoral fellow in Ho’s research group. Because of the large amount of available surface area, the clusters can carry a large amount of drug, nearly five times the amount of drug carried by conventional materials.

Liposomes and polymersomes, both spherical nanoparticles, currently are used for drug delivery. While effective, they are essentially hollow spheres loaded with an active drug ready to kill any cells, even healthy cells that are encountered as they travel to their target. Liposomes and polymersomes also are very large, about 100 times the size of nanodiamonds -- SUVs compared to the nimble nanodiamond clusters that can circulate throughout the body and penetrate cell membranes more easily.

Unlike many of the emerging nanoparticles, nanodiamonds are soluble in water, making them clinically important. “Five years ago while working in Japan, I first encountered nanodiamonds and saw it was a very soluble material,” said materials scientist Houjin Huang, lead author of the paper and also a post-doctoral fellow in Ho’s group. “I thought nanodiamonds might be useful in electronics, but I didn’t find any applications. Then I moved to Northwestern to join Dean and his team because they are capable of engineering a broad range of devices and materials that interface well with biological tissue. Here I’ve focused on using nanodiamonds for biomedical applications, where we’ve found success.

“Nanodiamonds are very special,” said Huang. “They are extremely stable, and you can do a lot of chemistry on the surface, to further functionalize them for targeting purposes. In addition to functionality, they also offer safety -- the first priority to consider for clinical purposes. It’s very rare to have a nanomaterial that offers both.”

“It’s about optimizing the advantages of a material,” said Ho, a member of the Lurie Cancer Center. “Our team was the first to forge this area -- applying nanodiamonds to drug delivery. We’ve talked to a lot of clinicians and described nanodiamonds and what they can do. I ask, ‘Is that useful to you?’ They reply, ‘Yes, by all means.’”

For their study, Ho and his team used living murine macrophage cells, human colorectal carcinoma cells and doxorubicin hydrochloride, a widely used chemotherapy drug. The drug was successfully loaded onto the nanodiamond clusters, which efficiently ferried the drug inside the cells. Once inside, the clusters broke up and slowly released the drug.

In the genetic studies, the researchers exposed cells to the bare nanodiamonds (no drug was present) and analyzed three genes associated with inflammation and one gene for apoptosis, or cell death, to see how the cells reacted to the foreign material. Looking into the circuitry of the cell, they found no toxicity or inflammation long term and a lack of cell death. In fact, the cells grew well in the presence of the nanodiamond material.

Developing a modular, nanoparticle drug delivery system

2007-10-05T15:38:00.000-07:00

There are two aspects to creating an effective drug: finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job.

With the support from a $478,000, five-year CAREER award from the National Science Foundation, Eva Harth is tackling the second part of this problem. She is creating a modular, multi-functional drug delivery system that promises simultaneously to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs.

Harth has taken a different approach from other researchers working on nanotechnology for drug development. Instead of trying to encapsulate drugs in nanoscale containers, she decided to create a nanoparticle that had a large number of surface sites where drug molecules could be attached. To do so, she adopted a method that uses extensive internal cross-linking to scrunch a long, linear molecule into a sphere about 10 nanometers in diameter, about the size of a protein. Nanoparticles like this are called nanosponges.

Hamm studies G proteins, arguably the most important signaling molecules in the cell. Scientists think that many diseases, including diabetes and certain forms of pituitary cancer, are caused by malfunctioning G proteins. She and Harth are collaborating on using the transporter to deliver peptides produced by G proteins that disrupt signaling pathways.

“Eva’s methods for drug delivery are very novel and versatile and can be adapted to delivery of proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful,” Hamm says.

She is now working with Hallahan to adapt her delivery system to carry cisplatinum, a traditional chemotherapy agent that is used to treat a number of different kinds of cancer but is highly toxic and has a number of unpleasant side effects.

By delivering the anti-cancer agent directly to the cancerous tissues, Eva’s system decreases the adverse effects on other tissues and increases its potency by delivering a higher concentration of the drug directly on the cancer, Hallahan explains.

“The people in my lab have tried at a number of different drug delivery systems and Eva’s works the best of those we’ve looked at,” Hallahan says.

Safer Light-Activated Nanoparticle Cancer Therapy

2007-09-28T09:08:00.000-07:00

Oncologists have long suspected that photodynamic therapy could find broader use if only there was some way to limit the accumulation of photosensitizer molecules to tumors, sparing healthy tissue from unintended damage. Now, using modified silica nanoparticles, a team of investigators at the State University of New York, Buffalo, has developed a photosensitizer delivery method that has the potential to target tumor cells specifically.

His group has used porous silica nanoparticles modified in such a way as to form a strong chemical bond between the nanoparticles and the photosensitizer molecules. When exposed to light, the permanently entrapped photosensitizer still produces reactive oxygen molecules that can diffuse out of the nanoparticles through their porous silica shells.

The investigators found, too, that human colon cancer cells readily take up the photosensitizer-loaded nanoparticles. More importantly, shining light on these cells resulted in their death.

Coated carbon nanotubes retain ability to bind to drugs and imaging agents

2007-09-28T09:05:00.000-07:00

In the quest to turn carbon nanotubes from nanoscale wonder into clinically useful drug and imaging agent delivery agents, researchers have often added polymer coatings to the outside of the nanotubes in order to render them biocompatible. Now, researchers at Stanford University have found that even when coated, carbon nanotubes retain the ability to bind extraordinarily large numbers of drug and imaging agent molecules in a stable yet reversible manner.

Reporting its work in the journal ACS Nano, a research team led by Hongjie Dai, Ph.D., an investigator in the Center for Cancer Nanotechnology Excellence Focused on Therapy Response, showed that polymer-coated single-walled carbon nanotubes spontaneously absorbed the cancer drug doxorubicin onto their surfaces when the drug was added to the nanotubes dissolved in water. The resulting construct contained approximately 50 to 60 percent doxorubicin by weight, far higher than the 8 to 10 percent obtained with either liposomes or dendrimers.

More SENS3 Reports

2007-09-25T14:49:00.000-07:00

Matthew S. O’Connor (okee, a.k.a. Dr. Okie) reports on the SENS3 conference on life extension at the Ouroboros website. Okee is currently a postdoctoral fellow at UC Berkeley, Bioengineering Department in the laboratory of Dr. Irina Conboy.

Biomedical remediation (essentially the brain-child of Aubrey de Grey) is moving along quickly.

Two teams have identified strains of bacteria capable of using 7-ketocholesterol (one precursor of the poorly defined lipofuscin) as energy. The next goal is to clone the genes. After that they want to purify the enzyme responsible and feed it to people and see if it will break down our lipofuscin.

Okee's issue:

is that they are trying to solve a problem that hasn’t been proved to be a problem yet. Lipofuscin accumulation has long been associated with aging in many tissues, but never (as far as I am aware) proved to be responsible for any illness, ailment, or disease. Now, don’t get me wrong, Aubrey makes an excellent argument for this being a serious problem with no traditional biomedical solution in sight, but it’s still just theory.

In Okee's opinion:
wound healing and artificial repair was the most provocative and promising aspect of the research at SENS 3.

Cato Laurencin has an approach called “regenerative engineering.”

Okee's comment:

It was amazing, however, to see someone actually using a few in something practical! In my opinion, this is the reality of regenerative medicine: an innovative surgeon combining technology and knowledge of biology to partially repair injuries such that they will heal as well, or better than they started.

Dr. Laurencin showed results from his work on 3D absorbable poly L-lactide (PLLA) scaffolds that seem to promote recovery from surgery much more efficiently than traditional methods. This is a microsphere-based scaffold, which promotes efficient invasion and engraftment of osteoblasts to help repair bone. He is also investigating surfaces with nano-scale grooves, which are more conducive to mesenchymal stem cell proliferation.

There is scarless repair of brain tissue using nanofibers to accelerate the healing:

Rutledge Ellis-Behnke spoke on his work with SAPNS: Self Assembling Peptide Nanofiber Scaffold. Essentially, he squirts a solution containing these nanofibers into wound sites and reportedly achieves amazing results. He reports dramatic recovery from serious brain injury: both scarless repair of bulk brain tissue removal and reinnervation. In addition, he claims that the nanofibers can dramatically stop bleeding in wounds (he showed video of this). These results are so dramatic that they are almost unbelievable.

From the research paper [they are stopping bleeding in the brain in 15 seconds]:

This novel therapy stops bleeding without the use of pressure, cauterization, vasoconstriction, coagulation, or cross-linked adhesives. The self-assembling solution is nontoxic and nonimmunogenic, and the breakdown products are amino acids, which are tissue building blocks that can be used to repair the site of injury. Here we report the first use of nanotechnology to achieve complete hemostasis in less than 15 seconds, which could fundamentally change how much blood is needed during surgery of the future.

Two groups and three speakers addressed the issue of aged muscle, muscle regeneration, and muscle stem cells.

One of the groups work supports the idea that muscle stem cells remain intrinsically young, even while their tissue ages around them. Another group revitalized old muscle stem cells.

A startup company, Sangamo, has developed gene editing, which different from gene therapy. It’s not introducing exogenous DNA into your cells, it’s editing your genomic DNA.

One drawback for Dr Cui GIFT method of cancer treatment is that it requires 10 donors for every recipient. I speculate, we will probably need to use telomeres and culturing of cells to increase the volume of cells for donation.

Quick and dirty advice for keeping nanotech clean

2007-09-25T14:37:00.001-07:00

IEEE Spectrum discusses how to keep nanoparticles safe

There is a growing body of evidence that nanotechnological chemicals and related substances could pollute the air, soil, and water and damage human health. Preliminary studies from Arizona State University suggest that nanoparticles accumulate in the food chain and could cause problems later on. There is an opportunity to deploy nanoparticles properly.

We need to look at nanotechnology broadly, anticipate its adverse effects, and prevent problems. Prudently avoiding a crisis is always better than trying to repair damage later on.

The IEEE Spectrum article is discussing nanotechnology to mean:

When we talk about nanotechnology, we mean that the materials involved exist as microscopic particles with at least one dimension that is between 1 and 100 nanometers. To put this in perspective, consider that the typical nanosize particle of titanium dioxide in sunscreen is 20 nm in diameter. The particle is a clump of about a million molecules. A grain of pollen is about 1000 times the size of this titanium dioxide nanoparticle; bacterial cells are around 100 times as large, and the width of a human hair is about 4000 times as great.

Nanotechnology refers to manufactured materials in the nanosize range, or to manufactured products containing these materials.

The health risks and concerns of nanoparticles:
In 2003, Chiu-wing Lam of NASA’s Johnson Space Center, in Houston, instilled carbon

nanotubes into the lungs of mice and reported that they triggered granulomas, or areas of inflammation. In a similar experiment, David Warheit at Dupont’s Haskell Laboratory for Toxicity and Industrial Medicine, in Newark, Del., found such inflammation in rats’ lungs in the same year. Perhaps most troubling of all, nanoparticles can make their way into the brain by passing from the nose through the blood-brain barrier, a membrane that protects the brain from chemicals in the blood while allowing oxygen, carbon dioxide, sugars, and certain amino acids to pass through unaltered.

In 2004, experiments by Eva Oberdörster, a lecturer in biological sciences at Southern Methodist University, in Dallas, found that the buckyball, a nanostructure made of carbon atoms, can penetrate the brains of bass via the gills. There, the nanoparticles trigger a reaction in brain enzymes called oxidative stress, a change in brain chemistry that indicates harm. Eva Oberdörster (a daughter of Günter) also discovered that buckyballs are toxic to daphnia, tiny freshwater fleas used to test toxicity in aquatic systems [see photo, “Aquatic Mine Canaries”]. The buckyballs did not clump together and sink harmlessly to the bottom of the test sites as researchers had expected.

Researchers are also concerned about persistence. Because of their small size and light weight, nanoparticles can stay aloft in the upper atmosphere much longer than coarse particulate air pollutants, and current filter technologies for controlling particles have holes that are a thousand times too big to trap nanoparticles. Nanoparticles may also bioaccumulate. For example, bacteria can ingest them, so the particles could become part of our food chain. And we know that chemical pollutants, like some pesticides, can also accumulate in the chain. At the moment, though, we don’t know what effect nanomaterials will have on the food supply.

Good things that are happening and green nanotechnology trends to continue:

One bright sign is that industry groups and government agencies are beginning to include concerns about nanotechnology in their long-term research planning. An encouraging new initiative is Green Nanotechnology, pioneered by the EPA and the Woodrow Wilson International Center for Scholars, in Washington, D.C. The two organizations are developing a framework and recommended practices that would help prevent manufacturers from releasing substances currently recognized as pollutants into the atmosphere, as well as prevent the manufacture of products containing nanomaterials that would knowingly harm the environment. The development of guidelines for Green Nanotechnology would let consumers or governments reward companies that are performing well, on the model of Energy Star, a joint program of the EPA and the Department of Energy. It sets guidelines for energy efficiency of consumer products and allows products that meet those guidelines to display Energy Star labels.

Recently, there was a small but significant victory: manufacturers of gold nanoparticles used for paint and, potentially, environmental cleanup and cancer treatment, developed a manufacturing method that eliminated the use of a toxic organic chemical and replaced it with water, reducing energy use at the same time.

Green Nano also means using nanotechnology itself to clean up production processes. The semiconductor industry can replace dangerous chemicals such as the perfluorooctane sulfonate polymers used in photo resists, antireflective coatings, and reagents with less toxic nano alternatives. Nanomembranes can filter out waste and pollutants in chemical processes. Nano-enabled sensors can improve process control and monitor emissions. Nanoproducts that improve energy efficiency, such as solar cells or better conducting materials, indirectly improve the environment through lower power-plant emissions.

Researchers set new record for brightness of quantum dots

2007-09-25T09:26:00.000-07:00

By placing quantum dots on a specially designed photonic crystal, researchers at the University of Illinois have demonstrated enhanced fluorescence intensity by a factor of up to 108. Potential applications include high-brightness light-emitting diodes, optical switches and personalized, high-sensitivity biosensors.

A quantum dot is a tiny piece of semiconductor material 2 to 10 nanometers in diameter (a nanometer is 1 billionth of a meter). When illuminated with invisible ultraviolet light, a quantum dot will fluoresce with visible light.

To enhance the fluorescence, Cunningham and colleagues at the U. of I. begin by creating plastic sheets of photonic crystal using a technique called replica molding. Then they fasten commercially available quantum dots to the surface of the plastic.

Quantum dots normally give off light in all directions. However, because the researchers’ quantum dots are sitting on a photonic crystal, the energy can be channeled in a preferred direction – toward a detector, for example.

While the researchers report an enhancement of fluorescence intensity by a factor of up to 108 compared with quantum dots on an unpatterned surface, more recent (unpublished) work has exceeded a factor of 550.

“The enhanced brightness makes it feasible to use photonic crystals and quantum dots in biosensing applications from detecting DNA and other biomolecules, to detecting cancer cells, spores and viruses,” Cunningham said. “More exotic applications, such as personalized medicine based on an individual’s genetic profile, may also be possible.”

Nanoparticle Vaccine Is Both More Effective And Less Expensive

2007-09-21T14:22:00.000-07:00

from Sciencedaily, bioengineering researchers from the EPFL in Lausanne, Switzerland, have developed and patented a nanoparticle that can deliver vaccines more effectively, with fewer side effects, and at a fraction of the cost of current vaccine technologies.

This technology may make it possible to vaccinate against diseases like hepatitis and malaria with a single injection. And at an estimated cost of only a dollar a dose, this technology represents a real breakthrough for vaccine efforts in the developing world.

Thanks to recent advances, an immune response can be triggered with just a single protein from a virus or bacterium. Recent research has also shown that the best way to get sustained immunity is to deliver an antigen directly to specialized immune cells known as dendritic cells (DCs). Current methods have trouble obtaining an adequate immune response with a single injection and can cause side effects or even be toxic.

EPFL professors Jeff Hubbell and Melody Swartz and PhD student Sai Reddy have engineered nanoparticles that completely overcome these limitations. At a mere 25 nanometers, these particles are so tiny that once injected, they flow through the skin's extracellular matrix, making a beeline to the lymph nodes. Within minutes, they've reached a concentration of DCs thousands of times greater than in the skin. The immune response can then be extremely strong and effective.

In addition, the EPFL team has also engineered a special chemical coating for the nanoparticles that mimics the surface chemistry of a bacterial cell wall. The DCs don't recognize this as a specific invader, but do know that it's something foreign, and so a low-level, generic immune reaction known as "complement" is triggered. This results in a particularly potent immune response without the risk of unpleasant or toxic side effects.

Cost and logistics are important factors, especially for use in developing countries. Unlike other nanoparticle vaccine technologies that degrade in water and thus require expensive drying and handling procedures, the EPFL team's nanoparticles won't degrade until they are in the body. They are in liquid form and don't require refrigeration, so preparation and handling costs are reduced, and they are easy to transport.

More study is required to achieve these goals," she adds, "but we have every reason to believe this technique could be in use within five years."

Roche-Ventana would further gene diagnostics and treatment

2007-09-20T17:30:00.000-07:00

Businessweek reports on a possible merger of Roche-Ventana

Swiss Pharmaceutical giant Roche Holdings (RMMBY ) caught Wall Street by surprise in June when it launched a $75-a-share hostile bid for Ventana Medical Systems (VMSI ). The Tucson company pulled in just $238 million last year selling tools that help doctors analyze tissue samples to diagnose cancer. Roche's bid values the company at about $3 billion.

What Roche and Ventana share is an intimate understanding of the next revolution in medicine. In the coming decade, pharmaceutical products--especially cancer drugs--will be created in tandem with diagnostic tests that tell doctors which patients are likely to benefit. Right now, physicians often feel they're flying blind. Each patient arrives at the hospital with a unique genetic makeup, which affects whether a prescribed drug will kill tumor cells, cause devastating side effects, or possibly do nothing at all. If a new generation of gene tests can help predict these different outcomes, patients will be spared expensive and unhelpful ordeals. The pool of target patients for many medications will also shrink. But if doctors are confident a drug will help somebody, they'll prescribe it aggressively, and insurers will be more likely to foot the bill.

Roche is the most ardent evangelist for this pairing of drugs with gene-based diagnostics--an approach called personalized medicine.

Ventana and Roche both are facing regulatory hurdles. At present, the Food & Drug Administration has separate channels for reviewing drugs and diagnostics, and no procedure for reviewing them in combination.

For experts like Abrahams, the logic in pairing tests and treatments is irrefutable.

Introduction to nanopharmaceuticals

2007-09-20T13:54:00.001-07:00

Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology.

A definition from the Academy of Pharmaceutical Sciences of Great Britain.

Nanopharmaceuticals represent an emerging field where the nanoscale element may refer to either the size of the drug particle or to a therapeutic delivery system. These therapeutic systems may be defined as a complex system consisting of at least two components, one of which is the active ingredient. In this field the concept of nanoscale is the range from 1 to 1,000nm. The definition includes polymer therapeutics, which share many characteristics with macromolecular prodrugs such as antibody conjugates of drugs.

The European Science Foundation definition.

Nanopharmaceuticals can be developed either as drug delivery systems or biologically active drug products.

This sub-discipline is defined as the science and technology of nanometre size scale complex systems, consisting of at least two components, one of which being the active ingredient. In this field the concept of nanoscale was seen to range from 1 to 1000 nm.

Nanopharmaceuticals as a big part of what nanomedicine is today. From the Ruth Duncan presentation.

Various kinds of nanoscale particles used for nanopharmaceuticals

Nanoparticles is a microscopic particle with at least one dimension less than 100 nm.

Liposomes is a spherical vesicle composed of a bilayer membrane. In biology, this specifically refers to a membrane composed of a phospholipid and cholesterol bilayer

Antibody conjugates
A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein, thereby conferring the immunological attributes of the carrier on the attached antigen. This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides for the prevention of invasive bacterial disease.

polymer therapeutics

From the Ruth Duncan presentation

Buckyballs and Nanotubes

Nanoemulsions is a type of emulsion in which the sizes of the particles in the dispersed phase are defined as less than 1000 nanometers. A nanoemulsion of soybean oil to create drops of 400-600 nanometers in diameter will kill many pathogens such as bacteria and viruses.

Quantum Dots is a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes, or excitons (bound pairs of conduction band electrons and valence band holes) in all three spatial directions. The confinement can be due to electrostatic potentials (generated by external electrodes, doping, strain, impurities), the presence of an interface between different semiconductor materials (e.g. in core-shell nanocrystal systems), the presence of the semiconductor surface (e.g. semiconductor nanocrystal), or a combination of these

Small quantum dots, such as colloidal semiconductor nanocrystals, can be as small as 2 to 10 nanometers, corresponding to 10 to 50 atoms in diameter and a total of 100 to 100,000 atoms within the quantum dot volume. Self-assembled quantum dots are typically between 10 and 50 nm in size. Quantum dots defined by lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in semiconductor heterostructures can have lateral dimensions exceeding 100 nm. At 10 nm in diameter, nearly 3 million quantum dots could be lined up end to end and fit within the width of a human thumb.

Dendrimers - Dendrimers are synthetic polymers, a thousand times smaller than cells. Dendrimers can be synthesized in various predetermined sizes, and can interact with biological agents by modifying their surface properties.

FURTHER READING
An article on nanopharmaceuticals and veterinary medicine

Presentation by Ruth Duncan on nanopharmaceuticals

A nanopharmaceuticals site

Launching nanoparticle drug delivery site

2007-09-20T11:15:00.000-07:00

Here is the start of my site devoted to nanoparticle drug delivery. I am providing it as a service so that fewer people will need to buy overpriced market reports on the same subject. I will also launch several other sites on near term nanotechnology subjects. My main website on future technology with a significant focus on advanced nanotechnology is advancednano

The Drug delivery is a multi-billion dollar business. Some calculate it as a 9.8 billion business. Led by the strong growth of biotechnology drugs requiring novel delivery technologies, the injectable/implantable drug delivery market reached revenues of $9.8 billion in 2006

Nanotechnology in drug delivery

A drug delivery website

Drug delivery stocks

The 9th annual drug delivery symposium coming Dec 16-20, 2007 is only about $600 versus $5000 or more for some market reports

Advance Nanotech Singapore Pte. Ltd. owns 75% of Nano Solutions Limited (Imperial College, London) which is developing Nanovindex. Nanovindex is a nanoparticle-hydrogel composites for drug delivery.

From 2005, 10Q

Nanotechnologies have already begun to change the scale and methods of drug delivery and hold huge potential for future developments in this area. Nanotechnology can provide new formulations and routes for drug delivery that broaden their therapeutic potential enormously by allowing the delivery of new types of medicine to previously inaccessible sites in the body. Novel composites incorporating nanoparticles are particularly exciting for these applications. A key to gaining competitiveness within the market is to develop next generation composites which are extremely sensitive to a variety of environmental stimuli. NanoVindex aims to achieve this by utilising expertise in rational peptide design to incorporate specific pH, enzymes and temperature triggers within the composites enabling a new level of control over the release of encapsulated drugs.

Technology

NanoVindex is seeking to develop a platform technology of nanoparticle-hydrogel composites for tailored drug delivery applications. The development shall leverage the research of Imperial College London in rational design of self-assembling peptide systems, control over the nanoscale organic/inorganic interface, and physiologically responsive bio-nano materials. Revenues to drug delivery companies were $1.3bn in 2002 and projected to increase to $6.7bn by 2012. With the focus evermore on emerging nanotechnologies and the improvements these may offer over more conventional systems, the market for new nanotechnologies in drug delivery is poised to be a multi-billion dollar arena. These technologies have the potential to revolutionise the pharmaceutical industry.

FURTHER READING
Abstract on Hydrogel-Nanofiber Composite Systems For Drug Delivery

2003 patent, Composite hydrogel drug delivery systems

google search of hydrgel composites drug delivery

Google search on nanoparticle drug delivery

Other drug delivery market studies by Kalorama