Zhang Xue, Lin Congcong, Lu Aiping, Lin Ge, Chen Huoji, Liu Qiang, Yang Zhijun, Zhang Hongqi
a School of Chinese Medicine , Hong Kong Baptist University , Hong Kong , China.
b Changshu Research Institute , Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone , Changshu , Jiangsu Province , China.
Drug Deliv. 2017 Nov;24(1):986-998. doi: 10.1080/10717544.2017.1340361.
A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.
肿瘤特异性脂质体成功的一个主要障碍是它们无法有效穿透肿瘤。在本研究中，我们将细胞穿透肽BR2整合到负载抗癌药物斑蝥素（CTD）的脂质体表面，以创建一个更高效、更有效地靶向肝癌（HCC）细胞的系统。比较负载脂质体对肝癌HepG2细胞和对照Miha细胞作用的体外细胞毒性试验表明，BR2修饰后，负载CTD的脂质体具有更强的抗癌作用。HepG2细胞和Miha细胞的细胞摄取结果进一步证实了BR2修饰脂质体穿透癌细胞的卓越能力。共定位研究表明，BR2修饰的脂质体可以进入肿瘤细胞并随后释放药物。通过评估HepG2肿瘤球体的穿透和抑制情况，与未修饰的脂质体相比，BR2脂质体具有更高的递送效率。体内生物分布研究和抗癌疗效结果显示，BR2修饰的脂质体在肿瘤部位有显著积累，并增强了肿瘤抑制作用。总之，BR2修饰的脂质体提高了药物对肝癌的抗癌效力。
