Mitochondria‐Targeted Photoredox Catalysis Activates Pyroptosis for Effective Tumor Therapy

材料科学 上睑下垂 纳米技术 催化作用 生物化学 细胞凋亡 化学 程序性细胞死亡
作者
Bin Zhao,Jingyi Ye,Zeyu Chen,Danyang Chen,Jiajue Chai,Zhongxu Luo,Xu Chen,Dan Shao,Qianjun He,Chunhai Fan,Huan Zhang,Honglu Zhang
出处
期刊:Advanced Functional Materials [Wiley]
被引量:2
标识
DOI:10.1002/adfm.202417681
摘要

Abstract The development of biocompatible and efficient photocatalytic redox systems to mimic bio‐photoreactors in living cells holds great potential for manipulating intracellular biochemical reaction processes and thus advancing tumor therapy. In this study, a mitochondria‐targeted photoredox catalyst, 2D vacancy‐rich molybdenum oxide nanosheets (Mt‐VR‐MoO 3 ) is presented. These nanosheets possess a high density of oxygen vacancies (19.2%) and exhibit strong photocatalytic redox activity under near‐infrared (NIR) light. Following a two‐step functionalization, Mt‐VR‐MoO 3 effectively disrupts mitochondrial electron flow in an oxygen‐independent manner upon irradiation with second near‐infrared (NIR‐II) light. This targeted disruption leads to on‐demand induction of substantial damage to tumor cell mitochondria, characterized by increased production of mitochondrial reactive oxygen species (mtROS) and the release of cytochrome c (Cyt c ), which collectively trigger the pyroptosis of cancer cells. The approach achieved tumor‐targeted photocatalytic eradication with high efficacy (tumor growth inhibition rate of 86.9%) in an orthotopic breast 4T1 murine tumor model, with no observable harm to normal organs. These findings provide inspiration for manipulating intracellular biochemical reactions using artificial photocatalytic materials, paving the way for pyroptosis activation as a promising approach in tumor therapy.
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