A polymer-(multifunctional single-drug) conjugate for combination therapy
A polymer-(multifunctional single-drug) conjugate for combination therapy
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用于联合治疗的聚合物-（多功能单药）缀合物
DOI：
10.1039/c5tb00576k
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发表时间：
2015
影响因子：
7
通讯作者：
Huang Yubin
中科院分区：
文献类型：
--
作者：
Zhou Dongfang;He Shasha;Cong Yuwei;Xie Zhigang;Chen Xuesi;Jing Xiabin;Huang Yubin
基于聚合物-药物偶联物的联合治疗是聚合物药物递送系统中令人兴奋的发展之一。具有两种或更多种连接的药物的单一聚合物载体是有利的，因为它提供了协同剂作用的平台。为了扩展使用单一聚合物-药物缀合物的联合治疗的概念，我们报告了聚合物-（多功能单一药物）缀合策略，其中三种不同的药物（铂、叠氮基自由基和DMC）和两种不同类型的治疗被合理地整合，然后缀合到两亲性嵌段共聚物。当这种聚合物-（多功能单一药物）缀合物通过内吞作用被癌细胞内化时，预期三种整合的药物在细胞外（UVA照射）和细胞内（内体/溶酶体）环境下被激活并以顺序方式执行治疗功能，以放大癌症治疗的信号，特别是在顺铂抗性癌细胞中。
Combination therapy based on polymer–drug conjugates is one of the exciting developments in polymeric drug delivery systems. A single polymer carrier with two or more drugs attached is advantageous because it provides a platform for synergistic agent action. To expand the concept of combination therapy using a single polymer–drug conjugate, we report a polymer–(multifunctional single-drug) conjugate strategy, in which three different drugs (platinum, azidyl radical and DMC) and two different types of therapies are rationally integrated and then conjugated to an amphiphilic block copolymer. When this polymer–(multifunctional single-drug) conjugate is internalized by cancer cells via endocytosis, the three integrated drugs are expected to be activated and execute therapeutic functions in a sequential fashion under extracellular (UVA irradiation) and intracellular (endosomes/lysosomes) environments to amplify the signals of cancer treatment, especially in cisplatin-resistant cancer cells.