H2S-Releasing Polymer Micelles for Studying Selective Cell Toxicity

We report the preparation of S-aroylthiooxime (SATO) functionalized amphiphilic block copolymer micelles that release hydrogen sulfide (H 2 S), a gaseous signaling molecule of relevance to various physiological and pathological conditions. The micelles release H 2 S 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 H 2 S impacts growth and proliferation of cancer cells; however, the limited control over H 2 S generation from inorganic sulfide sources results in conflicting reports. Therefore, we compare the cellular cytotoxicity of SATO-functionalized micelles, which release H 2 S in a sustained manner, to Na 2 S, which releases H 2 S in a single dose. Our results show that H 2 S-releasing micelles significantly reduce the survival of HCT116 colon cancer cells relative to Na 2 S, GYY4137, and a small molecule SATO, indicating that release kinetics may play an important role in determining toxicity of H 2 S toward cancer cells. Furthermore, H 2 S-releasing micelles are well tolerated by immortalized fibroblasts (NIH/3T3 cells), suggesting a selective toxicity of H 2 S toward cancer cells.