线粒体
氧化应激
钙
生物物理学
氧化磷酸化
化学
材料科学
生物化学
生物
冶金
作者
Weier Bao,Ming Liu,Jiaqi Meng,Siyuan Liu,Shuang Wang,Rongrong Jia,Yugang Wang,Guanghui Ma,Wei Wei,Tian Zhang
标识
DOI:10.1038/s41467-021-26655-4
摘要
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 (•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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