National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.
Int J Nanomedicine. 2012;7:4433-46. doi: 10.2147/IJN.S32053. Epub 2012 Aug 14.
Two methoxyl poly(ethylene glycol)-poly(L-histidine)-poly(L-lactide) (mPEG-PH-PLLA) triblock copolymers with different poly(L-histidine) chain lengths were synthesized. The morphology and biocompatibility of these self-assembled nanoparticles was investigated.
Doxorubicin, an antitumor drug, was trapped in the nanoparticles to explore their drug-release behavior. The drug-loaded nanoparticles were incubated with HepG2 cells to evaluate their antitumor efficacy in vitro. The effects of poly(L-histidine) chain length on the properties, drug-release behavior, and antitumor efficiency of the nanoparticles were investigated.
The nanoparticles were pH-sensitive. The mean diameters of the two types of mPEG-PH- PLLA nanoparticle were less than 200 nm when the pH values were 5.0 and 7.4. The nanoparticles were nontoxic to NIH 3T3 fibroblasts and HepG2 cells. The release of doxorubicin at pH 5.0 was much faster than that at pH 7.4. The release rate of mPEG(45)-PH(15)-PLLA(82) nanoparticles was much faster than that of mPEG(45)-PH(30)-PLLA(82) nanoparticles at pH 5.0.
The inhibition effect of mPEG(45)-PH(15)-PLLA(82) nanoparticles on the growth of HepG2 cells was greater than that of mPEG(45)-PH(30)-PLLA(82) nanoparticles when the concentration of encapsulated doxorubicin was less than 15 μg/mL.
合成了两种具有不同聚组氨酸链长的甲氧基聚乙二醇-聚（L-组氨酸）-聚（L-乳酸）（mPEG-PH-PLLA）三嵌段共聚物。研究了这些自组装纳米粒子的形态和生物相容性。
阿霉素是一种抗肿瘤药物，被包埋在纳米粒子中以探索其药物释放行为。将载药纳米粒子与 HepG2 细胞孵育，以评估其体外抗肿瘤功效。研究了聚组氨酸链长对纳米粒子性质、药物释放行为和抗肿瘤效率的影响。
纳米粒子具有 pH 敏感性。当 pH 值分别为 5.0 和 7.4 时，两种类型的 mPEG-PH-PLLA 纳米粒子的平均粒径均小于 200nm。纳米粒子对 NIH 3T3 成纤维细胞和 HepG2 细胞均无毒性。在 pH 5.0 时，阿霉素的释放速度明显快于 pH 7.4。在 pH 5.0 时，mPEG(45)-PH(15)-PLLA(82)纳米粒子的释放速率明显快于 mPEG(45)-PH(30)-PLLA(82)纳米粒子。
当包封阿霉素的浓度小于 15μg/mL 时，mPEG(45)-PH(15)-PLLA(82)纳米粒子对 HepG2 细胞生长的抑制作用大于 mPEG(45)-PH(30)-PLLA(82)纳米粒子。
