光动力疗法
光敏剂
化学
癌症研究
活性氧
结合
癌细胞
体内
线粒体
肿瘤微环境
生物物理学
药理学
癌症
生物化学
医学
生物
肿瘤细胞
内科学
数学分析
数学
生物技术
有机化学
作者
Xiaosheng Bai,Yan Lin,Lei Gong,Ji’an Duan,Xiaoduan Sun,Chang-Guang Wang,Zerong Liu,Jun Jiang,Xiangyu Zhou,Meiling Zhou,Zhirong Zhang,Zhongbing Liu,Jing Pei,Zhaohui Zhong
标识
DOI:10.1016/j.jconrel.2023.07.064
摘要
Photodynamic therapy, in which photosensitizers locally generate cytotoxic reactive oxygen species, can treat tumor tissue with minimal effects on surrounding normal tissue, but it can be ineffective because of the anoxic tumor microenvironment. Here we developed a strategy to inactivate the mitochondria of tumor cells in order to ensure adequate local oxygen concentrations for photodynamic therapy. We conjugated the photosensitizer 5-aminolevulinic acid to the lipophilic cation triphenylphosphine, which targets mitochondria. Then we packaged the conjugate into nanoparticles that were based on biocompatible bovine serum albumin and coated with folic acid in order to target the abundant folate receptors on the tumor surface. In studies in cell culture and BALB/c mice bearing MCF-7 xenografts, we found that the nanoparticles helped solubilize the cation-photosensitizer conjugate, prolong its circulation, and enhance its photodynamic antitumor effects. We confirmed the ability of the nanoparticles to target tumor cells and their mitochondria using confocal laser microscopy and in vivo assays of pharmacokinetics, pharmacodynamics, and tissue distribution. Our results not only identify a novel nanoparticle system for treating cancer, but they demonstrate the feasibility of enhancing photodynamic therapy by reducing oxygen consumption within tumors.
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