Co-delivery of doxorubicin and pheophorbide A by pluronic F127 micelles for chemo-photodynamic combination therapy of melanoma.
Co-delivery of doxorubicin and pheophorbide A by pluronic F127 micelles for chemo-photodynamic combination therapy of melanoma.
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DOI：
10.1039/c7tb03179c
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发表时间：
2018-05
期刊：
影响因子：
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通讯作者：
Chuangnian Zhang;Jimin Zhang;Yibo Qin;Huijuan Song;Pingsheng Huang;Weiwei Wang;Chun Wang;Chen Li-Che
中科院分区：
文献类型：
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作者：
Chuangnian Zhang;Jimin Zhang;Yibo Qin;Huijuan Song;Pingsheng Huang;Weiwei Wang;Chun Wang;Chen Li-Che
联合化疗和光动力疗法（PDT）是一种很有前途的策略，通过联合作用提高两种药物的抗癌疗效。在这项工作中，多柔比星（DOX）负载脱镁叶绿酸A（PheoA）改性Pluronic F127（F127）胶束（DOX/F127-PheoA胶束）的开发，用于黑色素瘤的联合化学-光动力学治疗。DOX/F127-PheoA胶束在尺寸和尺寸分布、zeta电位、表面形态、载药效率和药物释放性质方面进行表征。观察到DOX/F127-PheoA胶束是球形的，平均粒径为146.5nm，ζ电位为-3.2mV。共聚焦激光扫描显微镜显示DOX/F127-PheoA胶束被B16黑色素瘤细胞内化，并且能够将DOX和PheoA双重递送到肿瘤细胞中。在光照射下，DOX/F127-PheoA胶束可以在体外和体内产生活性氧（ROS）。CCK-8法测定DOX/F127-PheoA胶束对B16黑色素瘤细胞的体外细胞毒活性。还使用携带B16肿瘤的C57小鼠评估体内抗肿瘤功效，并静脉内施用DOX/F127-PheoA胶束。光照射下，DOX/F127-PheoA胶束与游离DOX和无光照射的DOX/F127-PheoA胶束相比，对肿瘤生长有明显的抑制作用。光照射下DOX/F127-PheoA胶束的平均肿瘤生长抑制率为73.5%，而无光照射的DOX/F127-PheoA胶束的平均肿瘤生长抑制率为42.3%，游离DOX的平均肿瘤生长抑制率为26.5%。这些结果表明，DOX/F127-PheoA胶束是一种通用的和有效的药物递送系统，用于组合化学-光动力学治疗黑色素瘤。
Combined chemotherapy and photodynamic therapy (PDT) is a promising strategy to enhance the anticancer efficacy of both drugs via combination effects. In this work, doxorubicin (DOX)-loaded pheophorbide A (PheoA)-modified Pluronic F127 (F127) micelles (DOX/F127-PheoA micelles) were developed for combined chemo-photodynamic therapy of melanoma. DOX/F127-PheoA micelles were characterized in terms of size and size distribution, zeta potential, surface morphology, drug loading efficiency, and drug-releasing properties. It was observed that the DOX/F127-PheoA micelles were spherical, with a mean particle size of 146.5 nm and a zeta potential of -3.2 mV. Confocal laser scanning microscopy showed that DOX/F127-PheoA micelles were internalized by B16 melanoma cells and capable of dual-delivery of both DOX and PheoA into tumor cells. Upon light irradiation, DOX/F127-PheoA micelles could generate reactive oxygen species (ROS) both in vitro and in vivo. The in vitro cytotoxic activity of DOX/F127-PheoA micelles in B16 melanoma cells were evaluated by CCK-8 assay. In vivo antitumor efficacy was also assessed using C57 mice bearing B16 tumors, and the DOX/F127-PheoA micelles were administrated intravenously. Under light irradiation, DOX/F127-PheoA micelles significantly inhibited tumor growth compared with free DOX and DOX/F127-PheoA micelles without light irradiation. The mean tumor growth inhibition rate of DOX/F127-PheoA micelles with light irradiation was 73.5%, compared with 42.3% for DOX/F127-PheoA micelles without light irradiation and 26.5% for free DOX. These results suggest that DOX/F127-PheoA micelles are a versatile and effective drug delivery system for combinational chemo-photodynamic therapy against melanoma.