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Access Type

WSU Access

Date of Award

January 2016

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

Arun K. Iyer

Abstract

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating the targeted delivery of Nrf2 siRNA to Hep G2 liver cancer cells overexpressing asialoglycoprotein receptors (ASGPRs). Our results demonstrate that the galactosamine decorated nanocarriers could effectively deliver Nrf2 siRNA into Hep G2 liver cancer cells resulting in efficient target gene knockdown, evincing its potential for targeted liver cancer therapy.

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