Title

Endolytic, pH-Responsive HPMA-b-(L-Glu) Copolymers Synthesized via Sequential Aqueous RAFT and Ring-Opening Polymerizations

Document Type

Article

Publication Date

10-1-2013

Department

Polymers and High Performance Materials

Abstract

A facile synthetic pathway for preparing block copolymers with pH-responsive L-glutamic acid segments for membrane disruption is reported. Aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization was first used to prepare biocompatible, nonimmunogenic poly[N-(2-hydroxypropyl)methacrylamide]. This macro chain transfer agent (CTA) was then converted into a macroinitiator via simultaneous aminolysis and thiol-ene Michael addition using the primary amine substituted N-(3-aminopropyl)methacrylamide. This macroinitiator was subsequently utilized in the ring-opening polymerization of the N-carboxyanhydride monomer of gamma-benzyl-L-glutamate. After deprotection, the pH-dependent coil-to-helix transformations of the resulting HPMA-b-(L-Glu) copolymers were monitored via circular dichroism spectroscopy. HPMA segments confer water solubility and biocompatibility while the L-glutamic acid repeats provide reversible coil-to-helix transitions at endosomal pH values (similar to 5-6). The endolytic properties of these novel [HPMA-b-(L-Glu)] copolymers and their potential as modular components in drug carrier constructs was demonstrated utilizing red blood cell hemolysis and fluorescein release from POPC vesicles.

Publication Title

Biomacromolecules

Volume

14

Issue

10

First Page

3793

Last Page

3799