Rapid Synthesis of a Lipocationic Polyester Library via Ring-Opening Polymerization of Functional Valerolactones for Efficacious siRNA Delivery


Authors: J. Hao, P. Kos, K. Zhou, J.B. Miller, L. Xue, Y. Yan, H. Xiong. S. Elkassih and D.J. Siegwart

Journal: Journal of the American Chemical Society

DOI: 10.1021/jacs.5b03429

Publication - Abstract

July 13, 2015

Abstract

The ability to control chemical functionality is an exciting feature of modern polymer science that enables precise design of drug delivery systems. Ring-opening polymerization of functional monomers has emerged as a versatile method to prepare clinically translatable degradable polyesters.1 A variety of functional groups have been introduced into lactones; however, the direct polymerization of tertiary amine functionalized cyclic esters has remained elusive. We report a strategy that enabled the rapid synthesis of >130 lipocationic polyesters directly from functional monomers without protecting groups. These polymers are highly effective for siRNA delivery at low doses in vitro and in vivo.

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