Defect engineering to tailor structure-activity relationship in biodegradable nanozymes for tumor therapy by dual-channel death strategies
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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.
I: Journal of Controlled Release, Bind 367, 2024, s. 557-571.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Defect engineering to tailor structure-activity relationship in biodegradable nanozymes for tumor therapy by dual-channel death strategies
AU - Su, Yutian
AU - Lv, Mengdi
AU - Huang, Zheng
AU - An, Nannan
AU - Chen, Yi
AU - Wang, Haoru
AU - Li, Zhengtu
AU - Wu, Shishan
AU - Ye, Feng
AU - Shen, Jian
AU - Li, Ao
N1 - Publisher Copyright: © 2024 Elsevier B.V.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Biodegradability
KW - Ferroptosis
KW - Multienzyme-mimicking catalytic activity
KW - Nanozymes
KW - Sustaining therapeutic activity
U2 - 10.1016/j.jconrel.2024.01.066
DO - 10.1016/j.jconrel.2024.01.066
M3 - Journal article
C2 - 38301929
AN - SCOPUS:85184005640
VL - 367
SP - 557
EP - 571
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -
ID: 382494847