A Self-Destroying Polycationic Polymer: Biodegradable Poly(4-hydroxy-l-proline ester)

化学 聚合物 水溶液 单体 高分子化学 低临界溶液温度 动态光散射 DNA 有机化学 化学工程 生物化学 共聚物 工程类 纳米颗粒
作者
Yong‐beom Lim,Young Hun Choi,Jong-Sang Park
出处
期刊:Journal of the American Chemical Society [American Chemical Society]
卷期号:121 (24): 5633-5639 被引量:176
标识
DOI:10.1021/ja984012k
摘要

A self-destroying, biodegradable, and polycationic polyester, poly(trans-4-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 slower 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, ζ potential, and nuclease resistance assay. These results show that PHP ester forms a strong complex with DNA by means of electrostatic interaction. Transfection of β-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.
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