氧化磷酸化
糖酵解
癌细胞
线粒体
化学
活性氧
癌症
癌症研究
细胞生物学
膜电位
生物化学
生物物理学
生物
新陈代谢
遗传学
作者
Fudan Dong,Qikun Jiang,Lingxiao Li,Tian Liu,Shiyi Zuo,Lin Gao,Mengna Fang,Yanlin Gao,Bingjun Sun,Cong Luo,He Zhang,Jin Sun
出处
期刊:Nano Research
[Springer Nature]
日期:2022-01-05
卷期号:15 (4): 3422-3433
被引量:17
标识
DOI:10.1007/s12274-021-3948-0
摘要
Mitochondrial bioenergy plays a vital role in the occurrence and development of cancer. Although strategies to impede mitochondrial energy supply have been rapidly developed, the anticancer efficacy is still far from satisfactory, mainly attributed to the hybrid metabolic pathways of mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. Herein, we construct a cancer cell membrane camouflaged nano-inhibitor, mTPPa-Sy nanoparticle (NP), which co-encapsulates OXPHOS inhibitor (mitochondrial-targeting photosensitizers: TPPa) and glycolysis inhibitor (syrosingopine (Sy)) for synergistically blocking the two different energy pathways. The mTPPa-Sy NPs exhibit precision tumor-targeting due to the high affinity between the biomimic membrane and the homotypic cancer cells. Under laser irradiation, the mitochondrial-targeting TPPa, which is synthesized by conjugating pyropheophorbide a (PPa) with triphenylphosphin, produces excessive reactive oxygen species (ROS) and further disrupts the OXPHOS. Interestingly, OXPHOS inhibition reduces O2 consumption and improves ROS production, further constructing a closed-loop OXPHOS inhibition system. Moreover, TPPa-initiated OXPHOS inhibition in combination with the Sy-triggered glycolysis inhibition results in lethal energy depletion, significantly suppressing tumor growth even after a single treatment. Our findings highlight the necessity and effectiveness of synergetic lethal energy depletion, providing a prospective strategy for efficient cancer therapy.
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