Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

• 来源期刊: 中国科学:化学（英文版）
• 年，卷（期）: 2018,（11）
• 页码范围: 1447-1459
• 页数: 13页
• 语种: 英文

摘要

Herein,new poly(ortho ester disulfide urethanes) (POEDU) and poly(ortho ester urethanes) (POEU) were successfully synthesized via polycondensation between active esters of 1,6-hexandiol (HD) and dual-stimuli-sensitive ortho ester disulfide diamine or pH-senstive ortho ester diamine.The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique.In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments.Doxorubicin (DOX) as a model antitumor drug was successfully incorporated into these nanospheres to give DOX-loaded nanoparticles (POEDU-DOX and POEU-DOX).In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol (DTT) and mildly acidic conditions.In addition,in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitumor effect than POEU-DOX did against both two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS).Finally,in a mice H22 tumor model,POEDU-DOX exhibited preferable antitumor capability.In conclusion,the pH and redox dual-stimuli-sensitive POEDU nanospheres can be superior drug carriers for cancer treatment.