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

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