A self-destroying polycationic polymer: Biodegradable poly(4-hydroxy-L-proline ester)
A self-destroying polycationic polymer: Biodegradable poly(4-hydroxy-L-proline ester)
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DOI：
10.1021/ja984012k
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发表时间：
1999-06-23
影响因子：
15
通讯作者：
Park, JS
中科院分区：
文献类型：
--
作者：
Lim, YB;Choi, YH;Park, JS
合成了一种自破坏、可生物降解的聚阳离子聚酯--聚反式-3-羟基-L-脯氨酸酯（PHP酯），并研究了该聚合物与聚阴离子DNA的相互作用。通过基质辅助激光解吸/电离飞行时间质谱法（MALDI-TOF MS）和通过测量作为聚合物骨架酯键降解产物形成的羧酸的pH变化，研究了聚合物在水溶液中的降解。MALDI-MS数据表明，聚合物在不到2 h内降解至小于完整聚合物分子量的一半。但在初始快速降解（1天内）后，鼓风机的降解速率是明显的。提出了一种初始阶段的自毁机制。聚合物逐渐降解到接近完成在3个月内在水溶液中的单体，羟脯氨酸，胶原蛋白的主要成分，这可以很容易地通过使用MALDI-MS检测。虽然聚合物在水溶液中降解非常快，它形成稳定的PHP酯/DNA复合物的静电相互作用时，聚合物与聚阴离子DNA溶液混合。通过电泳迁移率变动分析、动态光散射、xi电位和核酸酶抗性分析表征了DNA与聚合物形成自组装PHP酯/DNA复合物的缩合行为。这些结果表明，PHP酯与DNA通过静电相互作用形成强复合物。利用PHP酯/DNA复合物成功地将β-半乳糖苷酶基因转染到哺乳动物细胞中，显示了PHP酯作为生物可降解基因传递载体的可能性。
A self-destroying, biodegradable, and polycationic polyester, poly(trans-3-hydroxy-L-proline ester) (PHP ester), was synthesized, and the interaction of the polymer with polyanion DNA was investigated. Degradation of the polymer in aqueous solution was investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and by measuring the pH change as carboxylic acids are formed as products of the degradation of the polymer backbone ester bond. It was shown from MALDI-MS data that the polymer degraded to less than half of the intact polymer molecular weight in less than 2 h. But a Blower degradation rate after initial rapid degradation (within 1 day) was apparent. A self-destroying mechanism at the initial stage is proposed. The polymer was gradually degraded to near completion in 3 months in an aqueous solution to monomer, hydroxyproline, a major constituent of collagen, which could easily be detected by using MALDI-MS. Although the polymer degraded very quickly in an aqueous solution, it formed stable PHP ester/DNA complexes by electrostatic interaction when the polymer was mixed with the polyanionic DNA solution. The condensation behavior of DNA with the polymer to form self-assembled PHP ester/DNA complexes was characterized by electrophoretic mobility shift assay, dynamic light scattering, xi potential, and nuclease resistance assay. These results show that PHP ester forms a strong complex with DNA by means of electrostatic interaction. Transfection of beta-galactosidase gene into mammalian cell using PHP ester/DNA complexes was successful, showing the possibility of using PHP ester as a biodegradable gene delivery carrier.