Dr. Vinod Labhasetwar Abstract:

Translational Nanomedicine-Basic Mechanisms to Applications

Central to the applications of nanoparticles as an efficient carrier system for intracellular drug delivery is the need to understand their interactions with cell surface, their intracellular trafficking, and retention. We have previously demonstrated that PLGA-nanoparticles following cellular internalization via endocytic pathway undergo surface charge reversal (anionic to cationic) in the acidic pH of endo-lysosomes, thus facilitating their escape into the cytosolic compartment.

However, the subsequent studies showed that a significant fraction of nanoparticles are recycled out (undergo exocytosis) and only 15 percent of the internalized nanoparticles escape into the cytosolic compartment, thus limiting their efficiency for intracellular delivery of encapsulated therapeutics.

We have established a model to study nanoparticle-cellular interactions and the dynamics of intracellular trafficking of nanoparticles using Atomic Force (AFM) and Confocal microscopy.  In this presentation, the effect of surface properties of nanoparticles on endosomal escape of nanoparticles, their intracellular retention, and cytoplasmic delivery of encapsulated therapeutics will be discussed.

One of the objectives of the translational nanomedicine is to explore biomedical applications of nanoparticles to improve therapeutic outcomes. In this regard, we have been working on magnetic nanoparticles both for drug delivery and imaging applications. In addition, we are also exploring drug/gene delivery applications of biodegradable nanoparticles in cancer therapy and stroke.

The results of these studies will be discussed in the presentation.