title: H2S-Releasing Polymer Micelles for Studying Selective Cell Toxicity.
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.
authors.affiliation: Department of Chemistry, Macromolecules Innovation Institute, and Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Jeffrey C
authors.identifier: 0000-0002-9097-8680
authors.initials: JC
authors.lastname: Foster
authors.affiliation: Department of Chemistry, Macromolecules Innovation Institute, and Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Radzinski
authors.affiliation: Department of Biological Sciences and Biocomplexity Institute, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Biological Sciences and Biocomplexity Institute, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Carla V
authors.initials: CV
authors.lastname: Finkielstein
authors.affiliation: Department of Chemistry, Macromolecules Innovation Institute, and Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: John B
authors.identifier: 0000-0001-7984-5396
authors.initials: JB
authors.lastname: Matson
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry; D045325:HCT116 Cells; D006207:Half-Life; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D008823:Micelles; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009946:Organothiophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D013440:Sulfides / Q000737:chemistry
chemical_list: C529376:GYY 4137; D008823:Micelles; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D011108:Polymers; D013440:Sulfides; D003545:Cysteine; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: H2S donors; RAFT; controlled release; gasotransmitter; polymer amphiphiles