Chen Ming-Mao, Liu Yuan-Yuan, Su Guang-Hao, Song Fei-Fei, Liu Yan, Zhang Qi-Qing
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou.
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou.
Int J Nanomedicine. 2017 Jun 6;12:4225-4239. doi: 10.2147/IJN.S130861. eCollection 2017.
To design a rapid release liposomal system for cancer therapy, a NIR responsive bubble-generating thermosensitive liposome (BTSL) system combined with photothermal agent (Cypate), doxorubicin (DOX), and NHHCO was developed. Cypate/DOX-BTSL exhibited a good aqueous stability, photostability, and photothermal effect. In vitro release suggested that the amounts of DOX released from BTSL were obviously higher than that of (NH)SO liposomes at 42°C. After NIR irradiation, the hyperthermic temperature induced by Cypate led to the decomposition of NHHCO and the generation of a large number of CO bubbles, triggering a rapid release of drugs. Confocal laser scanning microscope and acridine orange staining indicated that Cypate/DOX-BTSL upon irradiation could facilitate to disrupt the lysosomal membranes and realize endolysosomal escape into cytosol, improving the intracellular uptake of DOX clearly. MTT and trypan blue staining implied that the cell damage of Cypate/DOX-BTSL with NIR irradiation was more severe than that in the groups without irradiation. In vivo results indicated that Cypate/DOX-BTSL with irradiation could dramatically increase the accumulation of DOX in tumor, inhibit tumor growth, and reduce systemic side effects of DOX. These data demonstrated that Cypate/DOX-BTSL has the potential to be used as a NIR responsive liposomal system for a rapid release of drugs in thermochemotherapy.
为设计一种用于癌症治疗的快速释放脂质体系统,开发了一种结合光热剂(塞帕替)、阿霉素(DOX)和NHHCO的近红外响应性气泡生成热敏脂质体(BTSL)系统。塞帕替/DOX-BTSL表现出良好的水稳定性、光稳定性和光热效应。体外释放表明,在42°C时,从BTSL释放的DOX量明显高于(NH)SO脂质体。近红外照射后,塞帕替诱导的高温导致NHHCO分解并产生大量CO气泡,引发药物快速释放。共聚焦激光扫描显微镜和吖啶橙染色表明,照射后的塞帕替/DOX-BTSL有助于破坏溶酶体膜并实现从内溶酶体逃逸到细胞质中,明显提高DOX的细胞内摄取。MTT和台盼蓝染色表明,近红外照射下塞帕替/DOX-BTSL对细胞的损伤比未照射组更严重。体内结果表明,照射后的塞帕替/DOX-BTSL可显著增加DOX在肿瘤中的蓄积,抑制肿瘤生长,并降低DOX的全身副作用。这些数据表明,塞帕替/DOX-BTSL有潜力用作近红外响应性脂质体系统,用于热化疗中药物的快速释放。