Disulfide Cross-Linked Polyurethane Micelles as a Reduction-Triggered Drug Delivery System for Cancer Therapy
Disulfide Cross-Linked Polyurethane Micelles as a Reduction-Triggered Drug Delivery System for Cancer Therapy
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二硫键交联聚氨酯胶束作为还原触发药物递送系统用于癌症治疗
DOI：
10.1002/adhm.201300308
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发表时间：
2014-05-01
影响因子：
10
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Yu, Shuangjiang;Ding, Jianxun;Chen, Xuesi
纳米级载体能够在血液循环中稳定地装载药物，并根据特定的触发因素在理想的部位释放有效载荷，这对智能药物输送系统非常有意义。为此，开发了一种新型的二硫核交联胶束，该胶束是由含有环二硫基团的聚乙二醇/聚氨酯嵌段共聚物通过硫-二硫交换反应交联而制成的。广谱抗癌药物阿霉素（DOX）作为模型药物被装载到胶束中。负载DOX的核心交联聚氨酯胶束（CCL-PUMs）的药物释放在正常磷酸盐缓冲盐水（PBS）中受到抑制，而在细胞内还原剂谷胱甘肽（GSH）的加入下，药物释放明显加速。值得注意的是，尽管与游离DOX或负载DOX的非交联聚氨酯胶束相比，负载DOX的CCL-PUMs在体外表现出较低的细胞毒性，但负载药物的CCL-PUMs在体内毒性降低的同时显示出最高的抗肿瘤功效。由于增强抗肿瘤疗效和减少毒副作用是有效癌症治疗的关键方面，新型还原反应性CCL-PUMs作为一种生物触发的癌症治疗药物传递系统可能具有巨大的潜力。
Nanoscale carriers that stably load drugs in blood circulation and release the payloads in desirable sites in response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, a novel type of disulfide core cross-linked micelles, which are facilely fabricated by cross-linking of poly(ethylene glycol)/polyurethane block copolymers containing cyclic disulfide moieties via a thiol-disulfide exchange reaction, are developed. A broad-spectrum anti-cancer drug, doxorubicin (DOX), is loaded into the micelles as a model drug. The drug release from the core cross-linked polyurethane micelles (CCL-PUMs) loaded with DOX is suppressed in normal phosphate buffer saline (PBS), whereas it is markedly accelerated with addition of an intracellular reducing agent, glutathione (GSH). Notably, although DOX-loaded CCL-PUMs display lower cytotoxicity in vitro compared to either free DOX or DOX-loaded uncross-linked polyurethane micelles, the drug-loaded CCL-PUMs show the highest anti-tumor efficacy with reduced toxicity in vivo. Since enhanced anti-tumor efficacy and reduced toxic side effects are key aspects of efficient cancer therapy, the novel reduction-responsive CCL-PUMs may hold great potential as a bio-triggered drug delivery system for cancer therapy.