Department of Pharmacy, Shengjing Hospital, China Medical University, Shenyang, China.
Drug Deliv. 2020 Dec;27(1):519-529. doi: 10.1080/10717544.2020.1745329.
Liver cancer is a malignant tumor with extremely high morbidity and mortality. At present, traditional chemotherapy is still the most commonly used therapeutic approach. However, serious side effects lead to the treatment of liver cancer is not ideal. Therefore, it is imperative to develop a new drug delivery system based on nanotechnology and liver cancer microenvironment. In this study, a pH/reduction/α-amylase multi-sensitive hydroxyethyl starch-10-hydroxy camptothecin micelles (HES-10-HCPT-SS-Ly) targeting over-expressed amino acid (AA) transporters on the surface of liver cancer cell by applying lysine were successfully synthesized. The prepared micelles showed regular structure, suitable particle size, and intelligent drug release property. Compared with conventional HES-10-HCPT micelles and 10-HCPT injection, HES-10-HCPT-SS-Ly micelles demonstrated better anti-proliferative capability toward human liver cancer Hep-G2 cells and greater antitumor efficiency against nude mouse with Hep-G2 tumor. These findings suggest that HES-10-HCPT-SS-Ly micelles may be a promising nanomedicine for treatment of liver cancer.
肝癌是一种发病率和死亡率极高的恶性肿瘤。目前，传统的化疗仍然是最常用的治疗方法。然而，严重的副作用导致肝癌的治疗效果并不理想。因此，迫切需要开发一种基于纳米技术和肝癌微环境的新型药物输送系统。本研究通过赖氨酸成功合成了一种 pH/还原/α-淀粉酶多重敏感羟乙基淀粉-10-羟基喜树碱胶束（HES-10-HCPT-SS-Ly），该胶束靶向肝癌细胞表面过表达的氨基酸（AA）转运体。所制备的胶束呈现出规则的结构、合适的粒径和智能的药物释放特性。与常规的 HES-10-HCPT 胶束和 10-HCPT 注射液相比，HES-10-HCPT-SS-Ly 胶束对人肝癌 Hep-G2 细胞表现出更好的增殖抑制能力，并对携带 Hep-G2 肿瘤的裸鼠表现出更大的抗肿瘤效率。这些发现表明，HES-10-HCPT-SS-Ly 胶束可能是治疗肝癌的一种有前途的纳米药物。
