CAREER: Development of Enzyme-Activated Nano-Conjugates for Targeted Drug Delivery

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

CBET-0747762, El-Sayed The goal of the project is to build an integrated interdisciplinary research and education program that focuses on the development of novel nano-sized polymeric drug delivery systems. The primary focus of this research is to develop new enzyme-activated polymer-drug conjugates for targeted delivery of chemotherapeutic agents for treatment of hepatic cancer. The rational design of these nano-conjugates will allow: i) the selection of appropriate polymeric carrier based on their physicochemical characteristics including size, molecular weight and net charge, ii) development of an innovative chemical linkage between the polymeric carrier and the attached drug molecules to allow spatial and temporal release of the loaded drug, and iii) optimizing the number of the attached drug molecules and targeting ligands. This systematic design and synthesis of these polymer-drug conjugates will produce highly selective and therapeutically effective drug delivery systems. The project will develop targeted, enzyme-activated, nano-sized, polymer-drug conjugates. These nano-conjugates have the potential to achieve tissue- and cell-selective drug delivery and to produce a spatially- and temporally-controlled drug release in specific sub-cellular compartments. These properties will result in higher therapeutic activities with minimal side effect, which will improve cancer therapy. This project will lead to the development of highly-specific polymer therapeutics for treatment of solid tumors particularly liver cancer. Successful completion of this research will provide critical support for innovative enzyme-activated conjugation strategies to emerge as a viable approach for delivery of therapeutic molecules. This enzyme-activated conjugation strategy has the potential to deliver a wide range of drug molecules to different organs within the body for treatment of latitude of life-threatening diseases. This research will positively impact the pharmaceutical and biotechnology industry as it presents a viable strategy to transform lead compounds into active therapies that improve healthcare. In addition, the proposed education plan will attract and train talented undergraduate and graduate students in the areas of nanotechnology and polymeric drug delivery systems. Furthermore, the PI plans to increase the number of women and minority students entering science and engineering disciplines through active mentoring and outreach efforts.