Catechol polymers for pH-responsive, targeted drug delivery to cancer cells.
Catechol polymers for pH-responsive, targeted drug delivery to cancer cells.
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DOI：
10.1021/ja203077x
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发表时间：
2011-08-10
影响因子：
15
通讯作者：
Messersmith, Phillip B.
中科院分区：
文献类型：
--
作者：
Su, Jing;Chen, Feng;Cryns, Vincent L.;Messersmith, Phillip B.
本研究采用一种新型细胞靶向、pH 敏感聚合物载体将抗癌药物硼替佐米 (BTZ) 递送至癌细胞。我们的策略基于 BTZ 与含儿茶酚聚合物载体的轻松缀合，这些聚合物载体旨在通过细胞表面受体介导的机制被癌细胞选择性吸收。本研究中用作构建模块的聚合物是聚乙二醇，之所以选择它是因为它能够减少与蛋白质和细胞的非特异性相互作用。儿茶酚部分因其能够以 pH 依赖性方式结合和释放 BTZ 等含硼酸盐治疗剂而被利用。在酸性环境中，例如在癌组织或亚细胞内体中，BTZ 与聚合物结合的儿茶酚基团解离，释放出游离药物，从而抑制蛋白酶体功能。癌细胞靶向配体生物素被呈现在聚合物载体上，以促进载药聚合物载体靶向进入癌细胞。我们的研究表明，与非靶向药物-聚合物缀合物相比，癌症靶向药物-聚合物缀合物显着增强了细胞摄取、蛋白酶体抑制和对乳腺癌细胞的细胞毒性。 pH 敏感的儿茶酚 - 硼酸盐结合机制提供了一种化学选择性方法来控制目标癌细胞中 BTZ 的释放，建立了一个可能在未来应用于其他含硼酸疗法以治疗多种疾病的概念。
A novel cell-targeting, pH-sensitive polymeric carrier was employed in this study for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on facile conjugation of BTZ to catechol-containing polymeric carriers that are designed to be taken up selectively by cancer cells through cell surface receptor-mediated mechanisms. The polymer used as a building block in this study was poly(ethylene glycol), which was chosen for its ability to reduce nonspecific interactions with proteins and cells. The catechol moiety was exploited for its ability to bind and release borate-containing therapeutics such as BTZ in a pH-dependent manner. In acidic environments, such as in cancer tissue or the subcellular endosome, BTZ dissociates from the polymer-bound catechol groups to liberate the free drug, which inhibits proteasome function. A cancer-cell-targeting ligand, biotin, was presented on the polymer carriers to facilitate targeted entry of drug-loaded polymer carriers into cancer cells. Our study demonstrated that the cancer-targeting drug–polymer conjugates dramatically enhanced cellular uptake, proteasome inhibition, and cytotoxicity toward breast carcinoma cells in comparison with nontargeting drug–polymer conjugates. The pH-sensitive catechol–boronate binding mechanism provides a chemoselective approach for controlling the release of BTZ in targeted cancer cells, establishing a concept that may be applied in the future toward other boronic acid-containing therapeutics to treat a broad range of diseases.
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影响因子：
20.3
作者：
Liu, Feng-Ting;Agrawal, Samir G.;Jia, Li
通讯作者：
Jia, Li
影响因子：
11.5
作者：
Zou, W;Yue, P;Sun, SY
通讯作者：
Sun, SY
DOI：
10.1016/s1054-3589(08)57003-7
发表时间：
2009-01-01
期刊：
CONTEMPORARY ASPECTS OF BIOMEDICAL RESEARCH: DRUG DISCOVERY
影响因子：
--
作者：
Ruggeri, Bruce;Miknyoczki, Sheila;Hui, Ai-Min
通讯作者：
Hui, Ai-Min
DOI：
10.2217/nnm.10.50
发表时间：
2010-07
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
MacEwan SR;Callahan DJ;Chilkoti A
通讯作者：
Chilkoti A
影响因子：
2.1
作者：
Yan, J;Springsteen, G;Wang, BH
通讯作者：
Wang, BH