One-pot synthesis of functional poly(amino ester sulfide)s and utility in delivering pDNA and siRNA

Yunfeng Yan, Lian Xue, Jason B. Miller, Kejin Zhou, Petra Kos, Sussana Elkassih, Li Liu, Atsushi Nagai, Hu Xiong, Daniel J. Siegwart

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The development of efficacious carriers is an important long-standing challenge in gene therapy. In the past few decades, tremendous progress has been made toward non-viral vectors for gene delivery including cationic lipids and polymers. However, there continues to be a need for clinically translatable polymer-based delivery carriers because they offer tunable degradation profiles and functional groups, diverse structures/morphologies, and scalability in preparation. Herein, we developed a library of 144 degradable polymers with varying amine and hydrophobic content via a facile method that involves thiobutyrolactone aminolysis and consequent thiol-(meth)acrylate or acrylamide addition in one-pot. The polymer platform was evaluated for pDNA and siRNA delivery to HeLa cells in vitro. Hydrophobically modified 5S, 2E1, 6CY1, 5CY2, and 2M1 grafted HEMATL polymers are capable of delivering pDNA depending on the chemical composition and the size of the polyplexes. Hydrophobically modified 5S and 2B grafted HEMATL and 5S grafted ATL polymers exhibit capability for siRNA delivery that approaches the efficacy of commercially available transfection reagents. Due to tunable functionality and scalable preparation, this synthetic approach may have broad applicability in the design of delivery materials for gene therapy.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalPolymer (United Kingdom)
Volume72
DOIs
StatePublished - Jan 3 2015

Keywords

  • Degradable polymers
  • Gene delivery
  • siRNA

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics

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