Recently, drug delivery systems have begun to utilize membrane-penetrating polymers and peptides to facilitate release of endocytosed therapeutic agents. Nucleic acid-based therapeutics such as siRNA must escape the endosome prior to fusion with lysosomes which contain degradative nucleases. A number of viruses utilize pH-responsive fusogenic peptides to penetrate cellular and endosomal membranes, but the use of viral peptides in drug delivery applications presents immunogenic concerns. This limitation has prompted the investigation of pH-responsive polymers capable of inducing hydrophobic membrane disruption within the pH range typically found in the endosome (pH=5-7).1 Bae and colleagues2 have prepared pH-tunable poly(acryloyl sulfonamide) (PAS) endosomolytic polymers with rapid and adjustable pH response behavior. However, the nature of the uncontrolled polymerization method used by Bae and coworkers limited their preparation of advanced well-defined polymer architectures. In this work, we report on the reversible addition-fragmentation chain transfer (RAFT) polymerization of sulfonamide-containing methacrylamide monomers to yield a library of polymers which undergo rapid and reversible pH-induced solubility changes in aqueous media across a range biologically relevant pH values. Current work entails the study of sulfonamide-substituent effects on solubility behavior of the resulting polymers and their application as potential endosomal membrane disrupters.1Holley, A. C.; Ray, J. G.; Wan, W.; Savin, D. A.; McCormick, C. L. Biomacromolecules 2013 , 14, 3793-3799.2Kang, H. C.; Bae, Y. H. Adv. Funct. Mater. 2007 , 17, 1263�1272.

RAFT polymerization of pH-responsive sulfonamide-functional methacrylamides

248th National Meeting (2014)

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