Defect engineering to tailor structure-activity relationship in biodegradable nanozymes for tumor therapy by dual-channel death strategies

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Yutian Su
  • Mengdi Lv
  • Zheng Huang
  • Nannan An
  • Yi Chen
  • Haoru Wang
  • Zhengtu Li
  • Shishan Wu
  • Feng Ye
  • Jian Shen
  • Ao Li

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.

OriginalsprogEngelsk
TidsskriftJournal of Controlled Release
Vol/bind367
Sider (fra-til)557-571
ISSN0168-3659
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Financial supports from the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, National Natural Science Foundation of China (82371979). The authors thank Prof. Hanne Mørck Nielsen from Department of Pharmacy, University of Copenhagen for the support of microfluidic chip.

Funding Information:
Financial supports from the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials , National Natural Science Foundation of China ( 82371979 ). The authors thank Prof. Hanne Mørck Nielsen from Department of Pharmacy, University of Copenhagen for the support of microfluidic chip.

Publisher Copyright:
© 2024 Elsevier B.V.

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