首页|Unimolecular Self-Assembled Hemicyanine-Oleic Acid Conjugate Acts as a Novel Succinate Dehydrogenase Inhibitor to Amplify Photodynamic Therapy and Eliminate Cancer Stem Cells
Unimolecular Self-Assembled Hemicyanine-Oleic Acid Conjugate Acts as a Novel Succinate Dehydrogenase Inhibitor to Amplify Photodynamic Therapy and Eliminate Cancer Stem Cells
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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 SO3-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.
National Engineering Research Center for Nanomedicine,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,P.R.China
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
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical,Huazhong University of Science and Technology,Wuhan 430074,P.R.China
Hubei Engineering Research Center for Biom
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National Research and Development Program of ChinaNational Research and Development Program of ChinaNational Research and Development Program of ChinaNational Science Foundation of ChinaNational Science Foundation of ChinaProgram for HUST Academic Frontier Youth TeamScientific Research Foundation of HUSTHCP Program for HUST
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