Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance  

作　　者：Haibao Peng Xingcai Zhang Peng Yang Jiaxu Zhao Wei Zhang Nianping Feng Wuli Yang Jing Tang 

机构地区：[1]Institute for Translational Brain Research,Fudan University,Shanghai,200032,China [2]State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Fudan University,Shanghai,200438,China [3]Department of Pharmaceutical Sciences,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [4]Department of Materials Science and Engineering,Stanford University,Stanford,CA,94305,United States [5]School of Engineering and Applied Sciences,Harvard University,Cambridge,MA,02138,United States [6]Engineering Research Center of Molecular-and Neuro-imaging of Ministry of Education,School of Life Science and Technology,Xidian University,710126,China

出　　处：《Bioactive Materials》2023年第1期1-11,共11页生物活性材料（英文）

基　　金：supported by China Postdoctoral Science Foundation(2020M681372);the National Natural Science Foundation of China(Grant Nos.51933002,81902756,82074279);Program of Shanghai Academic Research Leader(20XD1400400);the Natural Science Foundation of Shanghai(20ZR1458300);the Open Project of State Key Laboratory of Molecular Engineering of Polymers(No.K2021-19).

摘　　要：The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours.Ferroptosis,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse multidrug resistance.However,simultaneous delivery of the iron sources,ferroptosis inducers,drugs,and enhanced circulation carriers within matrices remains a significant challenge.Herein,we designed and fabricated a defect self-assembly of metal-organic framework(MOF)-red blood cell(RBC)membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer.Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron(III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process.The RBC membrane could camouflage the nanoplatform for longer circulation.Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione,amplify the reactive oxidative species oxidative stress,and enable remarkable anticancer properties.Our work provides an alternative strategy for overcoming multidrug resistance,which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis.This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.

关 键 词：Metal-organic framework Defect nanostructures Ferroptosis Membrane-camouflaged Multi-drug-delivery 

分 类 号：TB31[一般工业技术—材料科学与工程]