H2S‑Releasing Polymer Micelles for Studying Selective Cell Toxicity

• Published in: Molecular pharmaceutics 2017-04, Vol.14 (4), p.1300-1306
• Main Authors: Foster, Jeffrey C, Radzinski, Scott C, Zou, Xianlin, Finkielstein, Carla V, Matson, John B
• Format: Article
• Language: English
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.6b01117

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.