自噬
溶酶体
化学
安普克
细胞生物学
粒体自噬
三磷酸腺苷
葡萄糖氧化酶
细胞内
酶
生物化学
生物物理学
蛋白激酶A
生物
细胞凋亡
作者
Yifan Duan,Jianxin Wang,Jingjing Wang,Qiang Yang,Qiuye Zhang,Shiyu Lu,Sheng Zhao,Chunmei Chen,Yihao Sun,Jun Deng,Ji Zheng,Yang Cao,Hui Liu
标识
DOI:10.1016/j.cej.2022.136795
摘要
Excessive autophagy is a promising pathway to eliminate tumor cells, which causes excessive damages to overload the degradation capacity of lysosomes. Designing a nanosystem that can compromise the function of lysosomes and induce severe damages simultaneously is essential to activate excessive autophagy, but is still rarely explored. Herein, a dual-enzyme catalytic nanosystem with adenosine triphosphate (ATP) depletion capacity was developed for tumor elimination via the excessive autophagy pathway. This nanosystem consisted of polyvinyl pyrrolidone-stabilized polyaniline (PANI-PVP) core, Pt nanoparticles (NPs) decoration, and glucose oxidase (GOx) payload. After being internalized by tumor cells, this formed PANI-Pt-GOx-PVP NPs could escape from the lysosome through the proton sponge effect, causing lysosomal swelling and rupturing. The Pt-GOx dual-enzyme catalytic nanosystem consumes glucose to cause severe ATP shortage. This energy depletion microenvironment can not only generate intracellular damage during the GOx-mediated starvation process, but also induce mitophagy through AMPK activation. The increased accumulation of damage causes excessive autophagy, overloading the degradation capacity of lysosomes. In vivo data demonstrated that tumor growth tendency was significantly suppressed through this ATP depletion-induced excessive autophagy strategy.
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