CAS OpenIR
MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload
Bao, Weier1,2; Liu, Ming1; Meng, Jiaqi1,2; Liu, Siyuan1; Wang, Shuang2; Jia, Rongrong3; Wang, Yugang3; Ma, Guanghui2,4; Wei, Wei2,4; Tian, Zhiyuan1
2021-11-04
Source PublicationNATURE COMMUNICATIONS
Volume12Issue:1Pages:17
AbstractTargeting 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.
DOI10.1038/s41467-021-26655-4
Language英语
WOS KeywordMETAL-ORGANIC FRAMEWORKS ; CANCER-THERAPY ; PHOTOTRIGGERS ; TRANSITION ; EFFICIENCY ; APOPTOSIS ; CELLS
Funding ProjectNational 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 Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
Funding OrganizationNational Natural Science Foundation of China ; National Key R&D Program of China ; National Science and Technology Major Project of China
WOS IDWOS:000714754400011
PublisherNATURE PORTFOLIO
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/50951
Collection中国科学院过程工程研究所
Corresponding AuthorMa, Guanghui; Wei, Wei; Tian, Zhiyuan
Affiliation1.Univ Chinese Acad Sci, Sch Chem Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Dept Gastroenterol, Sch Med, Shanghai 200336, Peoples R China
4.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China
Recommended Citation
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.
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