新型多臂两亲性嵌段共聚物纳米粒子用于肝癌的靶向治疗

项目名称： 新型多臂两亲性嵌段共聚物纳米粒子用于肝癌的靶向治疗

项目编号： No.51203085

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 曾小伟

作者单位： 清华大学

项目金额： 25万元

中文摘要： 肝脏是人体的重要器官，肝癌等疾病导致了大量的死亡，严重威胁人类的健康。纳米靶向药物传递系统相对传统肝癌疗法具有高效、低毒、副作用小等优点。肝细胞表面存在大量去唾液酸糖蛋白受体(ASGPR)，可特异性识别半乳糖类化合物。本研究将从材料设计角度出发，以含多羟基的双季戊四醇(DPTOL)为引发剂合成一系列带氨基的新型多臂PLGA-b-PEG-NH2两亲性嵌段共聚物，由于没有改变材料的化学组分，因而可完全保留PLGA与PEG所固有的优异生物学性能。星型多臂的分子构型使纳米粒子具有更高载药量和更丰富的端氨基，可以携带比线性聚合物更多的靶向分子乳糖酸，将乳糖酸的高效肝靶向性和PLGA-b-PEG的优异性能相结合。通过肝靶向药物传递系统，研究纳米粒子在体内外细胞毒性、靶向效果和抑瘤效果，在分子和细胞水平上研究靶向机理，并对纳米粒子进行改进，以期获得具有我国自主知识产权的新型多功能靶向药物载体。

中文关键词： 靶向药物传递；癌症纳米技术；星型聚合物；肝癌；纳米医学

英文摘要： Liver is one of the most important and complex organs in the body. Liver cancer with a high mortality has led to serious threat to human health. As one of the main cancer treatment approaches, chemotherapy is often limited by the toxicity of anticancer drugs to normal tissues and cells. To reduce the side-effects and increase the therapeutic efficacy of anticancer drugs, targeted drug delivery system of nanoparticles is the most promising anticancer drug vectors. The asialoglycoprotein receptor (ASGPR) on mammalian hepatocytes has a special recognition of galactose, lactobionic acid, and lactose ligands provides a unique means for the development of liver targeted drug delivery systems. In this project, from the standpoint of materials design, the dipentaerythritol (DPTOL) is used as initiator, star-shaped copolymers with amino poly(lactide-ran-glycolide) -b-Polyethylene (6-PLGA-b-PEG-NH2) were synthesized by the ring-opening polymerization. The materials can fully retain the excellent inherent biological properties of PLGA and PEG because the chemistry components of materials do not change. The star-shaped block copolymers can generate more amino-terminated and have higher drug loading efficiency. Therefore, the nanoparticles which prepared by star-shaped copolymers can carry more targeted molecular lactobionic

英文关键词： Targeted drug delivery；Cancer nanotechnology；Star-shaped copolymer；Liver cancer；Nanomedicine