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

J Am Chem Soc. 2015 Jul 29;137(29):9206-9. doi: 10.1021/jacs.5b03429. Epub 2015 Jul 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Chemistry Techniques, Synthetic
  • Drug Carriers / chemistry*
  • HeLa Cells
  • Humans
  • Lactones / chemistry*
  • Lipids / chemistry*
  • Mice
  • Polyesters / chemistry*
  • Polymerization*
  • RNA, Small Interfering / chemistry*

Substances

  • Drug Carriers
  • Lactones
  • Lipids
  • Polyesters
  • RNA, Small Interfering