H2S-releasing polymer micelles for studying selective cell toxicity

Research output: Contribution to journalArticlepeer-review

Authors

  • Jeff Foster
  • S.C. Radzinski
  • X. Zou
  • C.V. Finkielstein
  • J.B. Matson

Colleges, School and Institutes

Abstract

We report the preparation of S-aroylthiooxime (SATO) functionalized amphiphilic block copolymer micelles that release hydrogen sulfide (H2S), a gaseous signaling molecule of relevance to various physiological and pathological conditions. The micelles release H2S in response to cysteine with a half-life of 3.3 h, which is substantially slower than a related small molecule SATO. Exogenous administration of H2S impacts growth and proliferation of cancer cells; however, the limited control over H2S generation from inorganic sulfide sources results in conflicting reports. Therefore, we compare the cellular cytotoxicity of SATO-functionalized micelles, which release H2S in a sustained manner, to Na2S, which releases H2S in a single dose. Our results show that H2S-releasing micelles significantly reduce the survival of HCT116 colon cancer cells relative to Na2S, GYY4137, and a small molecule SATO, indicating that release kinetics may play an important role in determining toxicity of H2S toward cancer cells. Furthermore, H2S-releasing micelles are well tolerated by immortalized fibroblasts (NIH/3T3 cells), suggesting a selective toxicity of H2S toward cancer cells.

Details

Original languageEnglish
Pages (from-to)1300-1306
Number of pages7
JournalMolecular Pharmaceutics
Volume14
Issue number4
Early online date16 Mar 2017
Publication statusPublished - 3 Apr 2017

Keywords

  • gasotransmitter, H2S donors, controlled release, polymer amphiphiles, RAFT