Smart drugs target disease

Author: John Monczunski

Traditional chemotherapy takes a scatter shot approach to cancer treatment. Since the chemo drugs are poison they kill cancer cells. Unfortunately, since the chemo drugs are poison they also kill healthy cells, which is why patients lose their hair and suffer kidney and liver damage as well as other harmful side effects.

It’s no surprise then that one of the main quests in pharmaceutical chemistry is to develop silver-bullet medicines, smart drugs that specifically target diseased cells while leaving healthy ones alone. The approach is being pursued not only to treat cancer but also for a wide variety of maladies, including allergies and other auto-immune diseases.

In pursuit of that silver bullet, Notre Dame’s Basar Bilgicer has been exploring the merits of a “Trojan horse” technique which employs incredibly tiny nanoparticle time-release capsules filled with the chemotherapy drug. These nanoparticles, which are 100,000 times smaller than the diameter of a human hair, are small enough to avoid being trapped in the filter of the kidneys and liver. In addition, they are surface modified to avoid attack from the body’s immune system..

Another drug design technique employed by the assistant professor of chemical and biomolecular engineering is to decorate the surface of the nanoparticles with molecular “recognition elements” for certain chemical receptors which are uniquely found on a tumor’s surface. It’s sort of a lock-and-key mechanism, in which the nanoparticles fit into the tumor.

By gaining a comprehensive understanding of the binding sites and how they work chemically and physically, Bilgicer hopes to engineer smarter drugs that use an array of nanoparticles targeted to different receptors. That capability would make it possible to deliver a variety of drugs working selectively and in harmony. And that would increase drug effectiveness while lowering side effects.

Currently, Bilgicer, who holds two patents with more on the way, is developing the approach to treat allergies and multiple myeloma, which, after lymphoma, is the second most common blood cancer. The myeloma work presents an extra degree of difficulty, he explains, because there is no tumor site per se. The diseased white blood cells are a moving target flowing through blood plasma.

In addition, he also has begun a research collaboration with Professor Katsuri Haldar, director of Notre Dame’s Center for Rare and Neglected Diseases, targeting malaria.

John Monczunski is an associate editor of Notre Dame Magazine.