Investigator: Matthew Kiesewetter, University of Rhode Island

Mentor: Geoffrey Bothun, University of Rhode Island

Scientific Theme: Cancer

Abstract: Multi-drug resistance represents a major hurdle in disease treatment. While some polymeric approaches aimed at overcoming multi-drug resistance have shown promise, they are largely based on synthetically costly procedures or materials that cannot be metabolized to benign products in vivo. Further, the FDA approval of polymers for cancer treatment modalities can represent a major hurdle to the clinical implementation of drug delivery polymers. By simply implementing polymer backbones that are composed of natural repeat units, one can obviate the requisite approval pathways and facilitate the rapid movement of the best treatment options from the laboratory to the clinic. Accordingly, the proposed research will develop a new class of highly functionalized polymers for use in drug delivery applications – built entirely from monomer units derived from nature. These constructs will be built with organocatalytic polymerization chemistry from hightly functionalized (Aim 1) thiocarbamate and (Aim 2) disulfide monomers. The constructs are composed of natural repeat units and will be biodegradable; they are designed to exhibit (Aim 1) attenuated release and (Aim 2) bolus release of therapeautic. The rate of release of drug will be evaluated with established fluorescence studies and cell uptake and release studies.

Human Health Relevance: Overcoming multi-drug resistance is a major hurdle in the treatment of cancer. Polymer-supported methods of drug delivery are one method to counteract this problem, but most of these polymers have long or even unlimited residence time in the body. This proposal seeks to develop methods to make polymers that are fully biocompatible. The polymers will be constructed of building blocks found in nature.