H2S-releasing polymer micelles for studying selective cell toxicity

Jeffrey C. Foster; Scott C. Radzinski; Xianlin Zou; Carla V. Finkielstein; John B. Matson

doi:10.1021/acs.molpharmaceut.6b01117

H₂S-releasing polymer micelles for studying selective cell toxicity

Jeffrey C. Foster, Scott C. Radzinski, Xianlin Zou, Carla V. Finkielstein, John B. Matson

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

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. (Graph Presented).

Original language	English
Pages (from-to)	1300-1306
Number of pages	7
Journal	Molecular Pharmaceutics
Volume	14
Issue number	4
DOIs	https://doi.org/10.1021/acs.molpharmaceut.6b01117
State	Published - Apr 3 2017
Externally published	Yes

Funding

This work was supported by the National Science Foundation (DMR-1454754 to J.B.M. and MCB-1517298 to C.V.F.) and the Virginia Tech Institute for Critical Technology and Applied Science (JFC12-256). We also thank 3M for support of this work through a Non-Tenured Faculty Award to J.B.M. We are grateful to Chris Winkler for assistance with TEM, Prof. Rick Davis for use of the DLS instrument, and Xiangping Fu for her excellent technical support.

Funders	Funder number
National Science Foundation	1454754, DMR-1454754, 1517298, MCB-1517298
3M
Institute for Critical Technologies and Applied Science, Virginia Tech	JFC12-256

Keywords

Controlled release
Gasotransmitter
HS donors
Polymer amphiphiles
RAFT

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acs.molpharmaceut.6b01117

Cite this

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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. (Graph Presented).",

keywords = "Controlled release, Gasotransmitter, HS donors, Polymer amphiphiles, RAFT",

author = "Foster, {Jeffrey C.} and Radzinski, {Scott C.} and Xianlin Zou and Finkielstein, {Carla V.} and Matson, {John B.}",

note = "Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

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doi = "10.1021/acs.molpharmaceut.6b01117",

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AU - Finkielstein, Carla V.

AU - Matson, John B.

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AB - 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. (Graph Presented).

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