Tumor-specific cyclic amplification of oxidative stress by disulfide-loaded fluoropolymer nanogels

Ruihong Xie; Peng Zhang; Liu Cai; Ranran Guo; Leyu Wang; Xiaozhong Qiu; Ye Tian

doi:10.1016/j.ejpb.2022.10.010

Tumor-specific cyclic amplification of oxidative stress by disulfide-loaded fluoropolymer nanogels

Eur J Pharm Biopharm. 2022 Nov:180:212-223. doi: 10.1016/j.ejpb.2022.10.010. Epub 2022 Oct 17.

Authors

Ruihong Xie¹, Peng Zhang², Liu Cai², Ranran Guo³, Leyu Wang², Xiaozhong Qiu⁴, Ye Tian⁵

Affiliations

¹ Biomaterials Research Center, School of Biomedical Engineering, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou 510515, China; Department of Mathematics and Physics, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China.
² Biomaterials Research Center, School of Biomedical Engineering, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou 510515, China.
³ Department of Orthopeadics, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
⁴ The Fifth Affiliated Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou 510999, China. Electronic address: qqiuxzh@163.com.
⁵ Biomaterials Research Center, School of Biomedical Engineering, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou 510515, China. Electronic address: tymty@smu.edu.cn.

PMID: 36265828
DOI: 10.1016/j.ejpb.2022.10.010

Abstract

Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. Herein, the effect of a disulfide, 2,2'-dithiobis(5-aminopyridine) (BAPS), is revealed on depleting glutathione (GSH) circularly and generating superoxide anion (O₂^•-) spontaneously to manipulate intracellular redox homeostasis. Thus, BAPS is able to work as an oxidative stress amplifier in cancer cells with high GSH concentrations and kill them efficiently. Moreover, leveraging a new class of water-soluble fluoropolymers poly(N-(2-((2,2,2-trifluoroethyl)sulfonyl)ethyl)acrylamide) (PFSNM), BAPS, together with oxygen, can be effectively delivered into hypoxic tumor cells through circulation and significantly inhibit the tumor growth. Therefore, BAPS-loaded PFSNM is an oxidative regulation nanosystem with remarkable therapeutic efficacy for chemodynamic therapy.

Keywords: Deplete GSH circularly; Disulfide; Fluoropolymer; Oxidative stress; Superoxide anion.

MeSH terms

Cell Line, Tumor
Disulfides*
Glutathione / metabolism
Humans
Nanogels
Neoplasms* / drug therapy
Oxidative Stress

Substances

Nanogels
Disulfides
Glutathione