摘要
Tumor hypoxia is one of the major factors restricting the photodynamic therapy(PDT)efficacy.To address this problem,we designed an arginine-peptide complex,namely Fluorenylmethoxycarbonyl-Leucine-Leucine-Leucine-Arginine-OH(Fmoc-L_(3)-Arg),which is able to co-assemble with 5,10,15,20-Tetrakis(4-hydroxyphenyl)porphyrin(THPP)into stable nanoparticles(NPs)with uniform and spherical shapes.The THPP/Fomc-L_(3)-Arg NPs were ultra-sensitive to tumorous acidic and oxidative conditions,and could rapidly release photosensitizers in tumor cells.Meanwhile,the co-loaded Fmoc-L_(3)-Arg could efficiently generate nitric oxide(NO),inhibiting mitochondrial cellular respiration and increasing oxygen in tumor cells to support the profound improvement of reactive oxygen species(ROS)yield and PDT efficacy.After intravenous injection,the THPP/Fomc-L_(3)-Arg NPs greatly accumulated at tumor tissue and significantly inhibited tumor growth upon irradiation.In conclusion,such an arginine-peptide complex-based nanoassembly addresses the inevitable problem of hypoxia-induced tumor resistance to PDT.
基金
supported by the National Natural Science Foundation of China(No.81773656)
the Liaoning Revitalization Talents Program(No.XLYC1808017)
the Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454).
作者简介
contributed equally to this work:Yanxian Hou;contributed equally to this work:Yafei Kuang;Address correspondence to:Jin Sun,sunjin@syphu.edu.cn。
