A multienzyme-mimicking nanoplatform induces disulfidptosis/cuproptosis/apoptosis for tumor therapyOA
The distinct characteristics of the tumor microenvironment(TME)provide great potential for valuable tumor-targeting therapies using enzymes.Herein,MOF-818 with a diameter of 139 nm is synthesized and exhibits multienzyme-mimicking activities,including peroxidase,catalase,glutathione oxidase,glucose oxidase,superoxide dismutase,and tyrosinase(TYR)-like activities.Based on these enzymatic activities,MOF-818 catalyzes an entire process that progresses through self-generated substrates and cyclic catalytic reactions,and notably induces TME remodeling.Synchronously,for the first time reported in nanozymes,MOF-818 activates the prodrug acetaminophen(APAP)through its TYR-like activity,further increasing reactive oxygen species accumulation.These features contribute to MOF-818’s antitumor activity by activating multiple combined programmed cell death pathways:apoptosis,disulfidptosis,and cuproptosis.The MOF-818 nanoplatform,3-methyladenine(3-MA),THP-1 cell membranes,and a fusion protein of Fc and TNF-related apoptosis-inducing ligand(Fc-TRAIL)were integrated to construct 3-MA@MOF-818@CM-Fc-TRAIL nanoparticles(3MCT NPs).These NPs target tumor cells and,when coupled with APAP,show efficient therapeutic effects with good biosafety.Our findings indicate that the MOF-818 could function as a multienzyme-mimetic scaffold for engineering targeted nanoplatforms that co-deliver combinatorial therapeutic agents,thereby enabling combined antitumor therapy.
Wei-Jie Sun;Jie Lin;Xiao-Kang Lu;Jin Fu;Jia-Wen Li;Hong-Min Zhu;Feng-Qi Zhou;Si-Ying Ma;Guo-Bao Ning;Bi-Lian Li;Hang Chen;Jie Li;Yu-Xun Lu;Xiang Lai;Lian Jin;Bai-Cheng Lu;Can-Peng Li;Ya-Ping Zhang;Hui Zhao
Bio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,China State Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650201,China Kunming College of Life Science,University of the Chinese Academy of Sciences,Kunming 650204,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaPathology Department,The Second People’s Hospital of Yunnan Province,Kunming 650021,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaState Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650201,China Kunming College of Life Science,University of the Chinese Academy of Sciences,Kunming 650204,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaSchool of Chemical Science and Technology,Yunnan University,Kunming 650500,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,China State Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650201,ChinaBio-X Center for Interdisciplinary Innovation,Yunnan University,Kunming 650500,China
医药卫生
nanozymestumor microenvironmentcancer enzyodynamic therapymetal-organic frameworksacetaminophencell death pathways
《National Science Review》 2026 (12)
P.61-77,17
supported by the National Natural Science Foundation of China(32371463 and 32160236)the Ma-jor Science and Technology Project of Yunnan Province(202302AE090022)the Postgraduate Supervisor Team of Yunnan Province,and the Yunnan Province High-level Scien-tific and Technological Talent and Innovative Team Selection Project(202005AC160008).
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