Redox-responsive biocompatible nanocarriers based on novel heparosan polysaccharides for intracellular anticancer drug delivery

• 作者: Guozhong Lv Huijie Zhang Jing Mao Jinghua Chen Kamel SAhmed Li Qin Lipeng Qiu Lu Ge Miaomiao Long Xiaotian Shan
• 来源期刊: 亚洲药物制剂科学(英文)
• 学科: 医学
• 关键词: HEPAROSAN Vitamin E SUCCINATE Redox-sensitive micelles Drug delivery
• 年，卷（期）: 2020,（1）
• 页码范围: 83-94
• 页数: 12页
• 分类号: R73

摘要

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosancystamine-vitamin E succinate(KSV) micelle system was constructed for intracellular delivery of doxorubicin(DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer(KV) was synthesized as control. DOX-loaded micelles(DOX/KSV) with an average particle size of 90–120 nm had good serum stability and redox-triggered depolymerization. In vitro drug release test showed that DOX/KSV micelles presented obvious redox-triggered release behavior compared with DOX/KV. Cytotoxicity and cell uptake were investigated using MGC80-3 tumor cells and COS7 fibroblast-like cells. The cell survival rate of blank micelles was more than 90%, and the cytotoxicity of DOX/KSV in MGC80-3 cells was higher than in COS7 cells, indicating that the carrier has better biocompatibility and less toxicity side effect. The cytotoxicity of DOX/KSV against MGC80-3 cells was significantly greater than that of free DOX and DOX/KV. Furthermore, compared with DOX/KV in MGC80-3 cells, DOX/KSV micelles uptook more anticancer drugs and then released DOX faster into the cell nucleus. The micelles were endocytosed by multiple pathways, but clathrin-mediated endocytosis was the main pathway. Therefore, heparosan polysaccharide could be a potential option as anticancer carrier for enhancing efficacy and mitigating toxicity.