Developing a modular, nanoparticle drug delivery system

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.