电荷翻转的聚酯树枝状大分子的合成、自组装及用于肿瘤细胞核的药物输送

Synthesis, Self-Assembly of Charge-Reversal Polyester Dendrimers for Cancer Cell Nuclear Drug Delivery

摘要: 以合成的具有电荷翻转能力的聚酯树枝状大分子(G4.5-DCA)为药物载体，包载了抗肿瘤药物阿霉素(DOX)。将G4.5-DCA(DOX)与两嵌段聚乙二醇-b-聚赖氨酸共聚物(PEG-b-PLL)静电自组装，得到了尺寸可控的载药纳米药粒。考察了该纳米药粒的粒径与形貌、药物的体外释放动力学、细胞中的亚分布以及细胞毒性。结果表明：该纳米药粒尺寸分布均一、具有很好的pH敏感药物释放特性；进入肿瘤细胞后，可将药物输送到细胞核中；与原药DOX相比该纳米药粒的细胞毒性显著提高。

Abstract: Polyester dendrimer (G4.5-DCA) with charge-reversal ability was synthesized as drug carrier for an anticancer drug doxorubicin (DOX). Nanoparticles with tunable sizes were prepared with G4.5-DCA(DOX) and PEG-b-PLL through electrostatic self-assembly. The size and morphology of the nanoparticles, drug release kinetics, subcellular distribution and cytotoxicity were characterized. Results showed that the nanoparticles were uniform in size and had pH-sensitive drug release behavior. Once the nanoparticles entered into a cell, they could deliver the drug into the nuclei. The nanoparticles showed superior cytotoxicity against cancer cells over free DOX.