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MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload

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机构: [1]School of Chemical Sciences, University of Chinese Academy of Sciences, 100049 Beijing, P. R. China. [2]State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, P. R. China. [3]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 200336 Shanghai, P. R. China. [4]School of Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, P. R. China.
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Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage. Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (center dot OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

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出版当年[2020]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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出版当年[2019]版:
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版:
Q1 MULTIDISCIPLINARY SCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者:
第一作者机构: [1]School of Chemical Sciences, University of Chinese Academy of Sciences, 100049 Beijing, P. R. China. [2]State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, P. R. China.
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通讯机构: [2]State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, P. R. China. [4]School of Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, P. R. China.
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