Synergetic lethal energy depletion initiated by cancer cell membrane camouflaged nano-inhibitor for cancer therapy  

作　　者：Fudan Dong Qikun Jiang Lingxiao Li Tian Liu Shiyi Zuo Lin Gao Mengna Fang Yanlin Gao Bingjun Sun Cong Luo Zhonggui He Jin Sun 

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Nano Research》2022年第4期3422-3433,共12页纳米研究（英文版）

基　　金：This work was financially supported by National Natural Science Foundation of China(No.81773656);Liaoning Revitalization Talents Program(No.XLYC1808017);Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454);National Postdoctoral Foundation of China(No.2021M693868).

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 O_(2) consumption and improves ROS production,further constructing a closed-loop OXPHOS inhibition system.Moreover,TPPa-initiated OXPHOS inhibition in combination with the Sytriggered 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.

关 键 词：synergetic lethality energy depletion mitochondria-targeting mitochondrial oxidative phosphorylation GLYCOLYSIS 

分 类 号：R73[医药卫生—肿瘤]