Unimolecular Self-Assembled Hemicyanine-Oleic Acid Conjugate Acts as a Novel Succinate Dehydrogenase Inhibitor to Amplify Photodynamic Therapy and Eliminate Cancer Stem Cells  

作　　者：Qiang Wang Tian Yang Shiyou Li Chen Xu Chong Wang Yuxuan Xiong Xing Wang Jiangling Wan Xiangliang Yang Zifu Li 

机构地区：[1]National Engineering Research Center for Nanomedicine,College of Life Science and Technology.Huazhong University of Science and Technology,Wuhan 430074,P.R.China [2]Key Laboratory of Molecular Biophysics of Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [3].3Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [4]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [5]Hubei Bioinformatics and Molecular Imaging Key Laboratory,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,P.R.China

出　　处：《Research》2024年第2期449-461,共13页研究（英文）

基　　金：supported by the National Research and Development Program of China(2018YFA0208900,2020YFA0710700,and 2020YFA0211200);the National Science Foundation of China(82172757 and 31972927);the Program for HUST Academic Frontier Youth Team(2018QYTD01);the Scientific Research Foundation of HUST(3004170130);the HCP Program for HUST.

摘　　要：Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells(CSCs).However,the innate drawbacks,including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors,have become bottlenecks for clinical applications of photodynamic therapy.Here,we develop a mitochondria-targeting hemicyanine-oleic acid conjugate(CyOA),which can self-assemble into supramolecular nanoparticles(NPs)without any exogenous excipients.CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia,resulting in 50.4-fold higher phototoxicity against breast cancer stem cells(BCSCs)compared to SO_(3)-CyOA NPs that cannot target to mitochondria.In 4T1 and BCSC tumor models,CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin.This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.

关 键 词：cyanine OXIDATIVE treatment 

分 类 号：R730.5[医药卫生—肿瘤]