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Monday, March 31, 2008

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

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.

Thursday, March 27, 2008

Nested' nanoparticles increase efficiency of drug delivery

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

Friday, March 21, 2008

Lipid Polymer Nanocontainers with controlled permeability


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

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

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.