Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes.
Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes.
复制标题
用于在培养的足细胞中直接装载和酸触发释放Bis-T-23的硼酸共聚物。
DOI：
10.1021/acsbiomaterials.8b01163
复制
发表时间：
2018-11
影响因子：
5.8
通讯作者：
Yilong Cheng;Gary W. Liu;Ritika Jain;J. Pippin;S. Shankland;S. Pun
中科院分区：
文献类型：
--
作者：
Yilong Cheng;Gary W. Liu;Ritika Jain;J. Pippin;S. Shankland;S. Pun
我们报告了一种用于触发释放 Bis-T-23 的酸可逆连接体，Bis-T-23 是一种用于肾脏疾病治疗的实验性小分子药物，可在疾病期间恢复足细胞形态。 Bis-T-23 含有儿茶酚，可与硼酸形成酸可逆的共价硼酸酯键。我们使用可逆加成断裂链转移聚合合成了含苯基硼酸的聚合物，该聚合物能够直接负载和溶解 Bis-T-23。由于硼酸酯键的可逆性，药物以其天然形式以 pH 依赖性方式释放。聚合物快速进入酸性区室并且不表现出细胞毒性，并且聚合物-药物缀合物成功地将 Bis-T-23 递送到培养的足细胞中。
We report an acid-reversible linker for triggered release of Bis-T-23, an experimental small molecule drug for kidney disease treatment that restores podocyte morphology during disease. Bis-T-23 contains catechols, which form an acid-reversible, covalent boronate ester bond with boronic acids. We synthesized phenylboronic acid-containing polymers using reversible addition-fragmentation chain transfer polymerization that were able to directly load and solubilize Bis-T-23. Because of the reversibility of the boronic ester bond, drug was released in its native form in a pH-dependent manner. The polymers rapidly trafficked into acidic compartments and did not exhibit cytotoxicity, and polymer-drug conjugates successfully delivered Bis-T-23 into cultured podocytes.