Precise Polymerization of a Highly Tumor Microenvironment-Responsive Nanoplatform for Strongly Enhanced Intracellular Drug Release
Precise Polymerization of a Highly Tumor Microenvironment-Responsive Nanoplatform for Strongly Enhanced Intracellular Drug Release
复制标题
高度肿瘤微环境响应性纳米平台的精确聚合，可显着增强细胞内药物释放
DOI：
10.1021/acsami.5b11569
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发表时间：
2016-03-09
影响因子：
9.5
通讯作者：
Zhou, Shaobing
中科院分区：
文献类型：
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作者：
Wang, Yi;Zhang, Lei;Zhou, Shaobing
众所周知，实现高含量的药物载体的响应基团对于实现快速细胞内药物释放的重要性;然而，很少有关于该主题的研究发表。在这里，我们提出了一个全新的策略来合成一个高度还原敏感的聚合物-药物缀合物，其中一个二硫键对应于每个所得的共聚物，通过一个精确的开环聚合的e-己内酯是由单保护的半胱氨酸引发。同时，抗癌药物阿霉素通过pH响应性腙键与聚合物化学缀合，这有效地防止了药物在血液循环中的过早释放。3-氨基苯基硼酸（PBA）靶向配体赋予主动靶向能力，其显著促进肿瘤细胞对纳米载体的特异性内化，从而导致对肿瘤细胞的优异细胞毒性。首次提出了精确聚合的概念，实现了纳米载体的多功能化。该研究有望启发开发高度环境响应的纳米平台，用于未来临床应用中的药物递送。
The importance of achieving a high content of responsive groups of drug carriers is well-known for achieving rapid intracellular drug release; however, very little research has been published on this subject. Here, we present an entirely new strategy to synthesize a highly reduction-sensitive polymer-drug conjugate with one disulfide bond corresponding to each resultant copolymer through a precise ring-opening polymerization of e-caprolactone that is initiated by a monoprotected cystarnine. Simultaneously, the anticancer drug doxorubicin is chemically conjugated to the polymer via pH-responsive hydrazone bonds, which effectively prevent premature drug release in the blood circulation. The 3-aminophenylboronic acid (PBA) targeting ligands endow an active-targeting ability that significantly prompts the specific internalization of nanocarriers by tumor cells and thus results in excellent cytotoxicity against tumor cells. The concept of precise polymerization is put forward to achieve multifunctional nanocarriers for the first time. This study is expected to inspire the development of a highly environment responsive nanoplatform for drug delivery in future clinical applications.