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Defect engineering to tailor structure-activity relationship in biodegradable nanozymes for tumor therapy by dual-channel death strategies.
Su, Yutian; Lv, Mengdi; Huang, Zheng; An, Nannan; Chen, Yi; Wang, Haoru; Li, Zhengtu; Wu, Shishan; Ye, Feng; Shen, Jian; Li, Ao.
Afiliação
  • Su Y; School of Chemistry and Chemical Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease
  • Lv M; National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing Normal University, Nanjing 210046, China.
  • Huang Z; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
  • An N; School of Chemistry and Chemical Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China.
  • Chen Y; School of Chemistry and Chemical Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China.
  • Wang H; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou 510120, China.
  • Li Z; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou 510120, China.
  • Wu S; School of Chemistry and Chemical Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China. Electronic address: shishanwu@nju.edu.cn.
  • Ye F; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou 510120, China.
  • Shen J; School of Chemistry and Chemical Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China; National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing Norma
  • Li A; Department of Ultrasound, Jiangsu Province People's Hospital, Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China.
J Control Release ; 367: 557-571, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38301929
ABSTRACT
Pursuing biodegradable nanozymes capable of equipping structure-activity relationship provides new perspectives for tumor-specific therapy. A rapidly degradable nanozymes can address biosecurity concerns. However, it may also reduce the functional stability required for sustaining therapeutic activity. Herein, the defect engineering strategy is employed to fabricate Pt-doping MoOx (PMO) redox nanozymes with rapidly degradable characteristics, and then the PLGA-assembled PMO (PLGA@PMO) by microfluidics chip can settle the conflict between sustaining therapeutic activity and rapid degradability. Density functional theory describes that Pt-doping enables PMO nanozymes to exhibit an excellent multienzyme-mimicking catalytic activity originating from synergistic catalysis center construction with the interaction of Pt substitution and oxygen vacancy defects. The peroxidase- (POD), oxidase- (OXD), glutathione peroxidase- (GSH-Px), and catalase- (CAT) mimicking activities can induce robust ROS output and endogenous glutathione depletion under tumor microenvironment (TME) response, thereby causing ferroptosis in tumor cells by the accumulation of lipid peroxide and inactivation of glutathione peroxidase 4. Due to the activated surface plasmon resonance effect, the PMO nanozymes can cause hyperthermia-induced apoptosis through 1064 nm laser irradiation, and augment multienzyme-mimicking catalytic activity. This work represents a potential biological application for the development of therapeutic strategy for dual-channel death via hyperthermia-augmented enzyme-mimicking nanocatalytic therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ferroptose / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ferroptose / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article