Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic gd ions chelated to the shell layer as a potential nanoscale IVIRI-visible delivery system
Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic gd ions chelated to the shell layer as a potential nanoscale IVIRI-visible delivery system
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DOI：
10.1021/bm700713p
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发表时间：
2008-01-01
影响因子：
6.2
通讯作者：
Li, Chun
中科院分区：
文献类型：
--
作者：
Zhang, Guodong;Zhang, Rui;Li, Chun
有很多兴趣在开发的纳米药物输送系统与MRI的可见性，以优化输送效率和治疗效果的图像引导下。在这里，我们报告的成功制造的纳米胶束的基础上，可生物降解的聚（L-谷氨酸）-b-聚乳酸（PG-b-PLA）嵌段共聚物与顺磁性Gd 3+离子螯合到他们的外壳。采用L-丙交酯阴离子聚合、谷氨酸苄酯N-羧酸酐开环聚合的顺序聚合反应合成了PG-b-PLA。金属螯合剂对氨基苯甲基二亚乙基三胺五（乙酸）（DTPA）很容易与聚（L-谷氨酸）的侧链羧酸共轭。所得共聚物在pH 7.4下在水溶液中形成平均直径为230 nm的球形胶束。PG（DTPA）-b-PLA胶束的粒径随pH值的升高而减小。螯合到胶束壳层的DTPA-Gd显示出比小分子量MRI造影剂显著更高的自旋晶格弛豫率（r（1）），表明水分子可以容易地接近胶束中的Gd离子。由于壳层中存在多个羧酸官能团，基于可生物降解PG（DTPA-Gd）-b-PLA的聚合物胶束可能是用于开发MRI可见的、靶向的纳米级药物递送系统的合适平台。
There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly(L-glutamic acid)-b-polylactide (PG-b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG-b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly(L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)-b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r(1)) than a small-niolecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)-b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.