Department of Pharmacy and Central Laboratory, Fengxian Hospital, Southern Medical University, 6600 Nanfeng Road, Shanghai 201499, China.
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Biosensors (Basel). 2021 Aug 30;11(9):306. doi: 10.3390/bios11090306.
Owing to poor aqueous solubility and low delivery efficiency, most of anti-cancer chemodrugs depend on various smart drug delivery platforms to enhance the treatment efficacy. Herein, a stimuli-responsive supramolecular drug delivery system (SDDS) is developed based on polymeric cyclodextrins (PCD) which crosslinked by stimuli-cleavable drug dimers via host-guest interaction. PEGylated PCD was precisely controlled synthesized by ring-opening polymerization and azide-alkyne click chemistry, and two doxorubicins (DOX) were linked with a disulfide bond to form a drug dimer (ss-DOX). They then co-assembled into supramolecular micelles. Drug dimers were utilized as cross-linkers to stabilize the micelles. The drug loading efficiency was very high that could be up to 98%. The size and morphology were measured by DLS and TEM. Owing to the disulfide bonds of drug dimers, these supramolecular micelles were dissociated by treating with dithiothreitol (DTT). In the meanwhile, the free DOXs were recovered and released from cavities of cyclodextrins because of dynamic equilibrium and hydrophilicity changes. The release profile was studied under mimic physiological conditions. Furthermore, in vitro cytotoxicity study showed excellent anti-cancer efficacy of reduced-responsive supramolecular polymeric micelles. Therefore, it can be served as a safe and stimuli-responsive SDDS for cancer therapy.
由于抗癌化疗药物的水溶性差和递送效率低，大多数都依赖于各种智能药物递送平台来提高治疗效果。在此，我们开发了一种基于通过主客体相互作用交联的刺激响应性超分子药物递送系统（SDDS）。通过开环聚合和叠氮-炔点击化学精确控制合成了聚环糊精（PCD），并用二硫键将两个阿霉素（DOX）连接起来形成药物二聚体（ss-DOX）。然后它们共同组装成超分子胶束。药物二聚体被用作交联剂来稳定胶束。药物负载效率非常高，可达 98%。通过 DLS 和 TEM 测量了其尺寸和形态。由于药物二聚体的二硫键，这些超分子胶束可以通过二硫苏糖醇（DTT）处理进行解离。同时，由于动态平衡和亲水性变化，游离的 DOX 从环糊精的空腔中被释放出来。在模拟生理条件下研究了释放情况。此外，体外细胞毒性研究表明，还原响应性超分子聚合物胶束具有优异的抗癌功效。因此，它可以作为一种安全且具有刺激响应性的 SDDS 用于癌症治疗。
