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

文献类型：期刊论文

作者Bao, Weier2,3; Liu, Ming2; Meng, Jiaqi2,3; Liu, Siyuan2; Wang, Shuang3; Jia, Rongrong1; Wang, Yugang1; Ma, Guanghui3,4; Wei, Wei3,4; Tian, Zhiyuan2
刊名NATURE COMMUNICATIONS
出版日期2021-11-04
卷号12期号:1页码:17
DOI10.1038/s41467-021-26655-4
英文摘要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.
WOS关键词METAL-ORGANIC FRAMEWORKS ; CANCER-THERAPY ; PHOTOTRIGGERS ; TRANSITION ; EFFICIENCY ; APOPTOSIS ; CELLS
资助项目National Natural Science Foundation of China[22077121] ; National Natural Science Foundation of China[21773241] ; National Natural Science Foundation of China[32030062] ; National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[U2001224] ; National Key R&D Program of China[2017YFA0207900] ; National Science and Technology Major Project of China[2018ZX10301-1-03-003]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000714754400011
资助机构National Natural Science Foundation of China ; National Key R&D Program of China ; National Science and Technology Major Project of China
源URL[http://ir.ipe.ac.cn/handle/122111/50950]  
专题中国科学院过程工程研究所
通讯作者Ma, Guanghui; Wei, Wei; Tian, Zhiyuan
作者单位1.Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Dept Gastroenterol, Sch Med, Shanghai 200336, Peoples R China
2.Univ Chinese Acad Sci, Sch Chem Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
4.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Bao, Weier,Liu, Ming,Meng, Jiaqi,et al. MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload[J]. NATURE COMMUNICATIONS,2021,12(1):17.
APA Bao, Weier.,Liu, Ming.,Meng, Jiaqi.,Liu, Siyuan.,Wang, Shuang.,...&Tian, Zhiyuan.(2021).MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload.NATURE COMMUNICATIONS,12(1),17.
MLA Bao, Weier,et al."MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload".NATURE COMMUNICATIONS 12.1(2021):17.

入库方式： OAI收割

来源：过程工程研究所

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