Development of a Shape-Controlled H2S Delivery System Using Epoxide-Functional Nanoparticles

Sul Hwa Yu, Lars Esser, Song Yang Khor, Danielle Senyschyn, Nicholas A. Veldhuis, Michael R. Whittaker, Francesca Ercole, Thomas P. Davis, John F. Quinn

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Hydrogen sulfide (H 2 S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H 2 S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H 2 S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H 2 S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H 2 S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H 2 S inside cells, upon exposure to biologically relevant endogenous thiol levels.

Original languageEnglish
Pages (from-to)1982–1993
Number of pages12
JournalJournal of Polymer Science, Part A: Polymer Chemistry
Volume57
Issue number18
DOIs
Publication statusPublished - 2019

Keywords

  • acyl-protected perthiol groups
  • block copolymers
  • drug delivery systems
  • hydrogen sulfide
  • nanoparticles
  • nanoparticulate donor
  • polymerization-induced self-assembly
  • postpolymerization modification
  • spherical and worm-like nanoparticulate donors
  • thiol

Cite this