Targeted delivery of cancer therapeutics offers an exciting new opportunity for utilization of controlled polymerization techniques. However, a major obstacle in achieving the desired therapeutic effect is facilitating endosomal release of active agents following endocytosis. Peptides and pH-responsive polymers have been utilized as a means of triggering endosomal release via phase transition-induced membrane disruption. Unfortunately, the fidelity by which the pKa of these polymers/peptides can be varied is limited, such that it reduces their versatility in altering the phase transition point to best match the endosomal pH of a particular cell-type. Herein, we report the controlled polymerization of a library of methacryloylsulfonamide derivatives via reversible addition-fragmentation chain transfer (RAFT) polymerization that exhibit a range of physiologically relevant pKa's. Polymerization control was observed by noting the low polydispersity indices of the polymers along with the linear progression of Mn with time during the polymerizations. The pH-dependent phase transition behavior of the polymers was tunable by varying the �R-group� of the sulfonamide, thus altering the pKaof the resulting polymer. Future work includes pH-dependent hemolysis studies to determine which sulfonamide derivatives promote endosomal disruption under physiological conditions.

Tunable pH-responsive sulfonamide-based polymers via RAFT as potential mediators of endosomal drug release

245th National Meeting (2013)

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