Redox-active polyphenol nanoparticles deprive endogenous glutathione of electrons for ROS generation and tumor chemodynamic therapy

Yifei Wang; Jia Wang; Yunke Jiao; Kangli Chen; Tianhao Chen; Xinping Wu; Xingwu Jiang; Wenbo Bu; Changsheng Liu; Xue Qu

doi:10.1016/j.actbio.2023.09.037

Redox-active polyphenol nanoparticles deprive endogenous glutathione of electrons for ROS generation and tumor chemodynamic therapy

Acta Biomater. 2023 Dec:172:423-440. doi: 10.1016/j.actbio.2023.09.037. Epub 2023 Sep 30.

Authors

Yifei Wang¹, Jia Wang², Yunke Jiao¹, Kangli Chen¹, Tianhao Chen¹, Xinping Wu³, Xingwu Jiang⁴, Wenbo Bu⁵, Changsheng Liu¹, Xue Qu⁶

Affiliations

¹ Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, PR China.
² State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Key Laboratory for Advanced Materials and Joint International Research Laboratory for Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Centre for Computational Chemistry and Research Institute of Industrial Catalysis, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
³ State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Key Laboratory for Advanced Materials and Joint International Research Laboratory for Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Centre for Computational Chemistry and Research Institute of Industrial Catalysis, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China. Electronic address: [email protected].
⁴ Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, PR China. Electronic address: [email protected].
⁵ Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, PR China.
⁶ Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, PR China; Wenzhou Institute of Shanghai University, Wenzhou 325000, PR China; Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai 200237, PR China. Electronic address: [email protected].

PMID: 37778486
DOI: 10.1016/j.actbio.2023.09.037

Abstract

Chemodynamic therapy (CDT) based on generating reactive oxygen species (ROS) is promising for cancer treatment. However, the intrinsic H₂O₂ is deficient for CDT, and glutathione (GSH) eliminates ROS to protect tumor cells from ROS cytotoxicity. Herein, we propose a strategy to switch the electron flow direction of GSH for O₂ reduction and ROS generation rather than ROS clearance by using P(DA-Fc) nanoparticles, which are polymerized from ferrocenecarboxylic acid (Fc) coupled dopamine. P(DA-Fc) NPs with phenol-quinone conversion ability mimic NOX enzyme to deprive electrons from GSH to reduce O₂ for H₂O₂ generation; the following •OH release can be triggered by Fc. Semiquinone radicals in P(DA-Fc) are significantly enhanced after GSH treatment, further demonstrated with strong single-electron reduction ability by calculation. In vitro and in vivo experiments indicate that P(DA-Fc) can consume intrinsic GSH to produce endogenous ROS; ROS generation strongly depends on GSH/pH level and eventually causes tumor cell death. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to ROS producer, explores new roles of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve the efficiency of CDT. STATEMENT OF SIGNIFICANCE: P(DA-Fc) nanoparticles performing tumor microenvironment response capacity and tumor reductive power utilize ability were fabricated for CDT tumor suppression. After endocytosis by tumor cells, P(DA-Fc) deprived GSH of electrons for H₂O₂ and •OH release, mimicking the intrinsic ROS production conducted by NADPH, further inducing tumor cell necrosis and apoptosis. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to producer, explores new functions of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve CDT efficiency.

Keywords: Electron transporting; GSH function reverse; NOX enzyme-like ROS generator; Polyphenol-based CDT nanomaterial; Redox activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Drug Carriers
Electrons
Glutathione
Humans
Hydrogen Peroxide
Nanoparticles*
Neoplasms* / drug therapy
Oxidation-Reduction
Polyphenols / pharmacology
Reactive Oxygen Species
Tumor Microenvironment

Substances

Reactive Oxygen Species
Polyphenols
Hydrogen Peroxide
Drug Carriers
Glutathione