聚酰胺-胺树状大分子靶向给药系统的研究进展

Research progress of polyamidoamine dendrimer in targeting drug delivery system

靶向给药系统(targeting drug delivery system,TDDS)能够选择性作用于病变部位,控制药物的分布与释放,提高药效和降低毒副作用,已成为癌症治疗领域的研究热点之一。聚酰胺-胺树状大分子(polyamidoamine dendrimer,PAMAMD)是一种新近发展起来的纳米级药物载体,多分枝、单分散性、三维结构和主-客体包裹能力使其可作为药物基因载体和影像试剂。PAMAMD丰富的末端功能团能同时连接各种具有特异选择性的靶向配基,再通过包裹作用或化学偶联作用将药物或治疗基因载入,最后将药物和治疗基因带到病变部位释放从而实现靶向治疗。这种以PAMAMD为基础制备的纳米靶向给药系统具有较小的粒径,强的高通透高滞留(enhanced permeability and retention,EPR)效应和低毒性等特点。本文概述了各种靶向配基修饰的PAMAMD的应用研究进展,并展望了今后的研究方向。

Targeting drug delivery system （TDDS） is one of the most concerned research fields in cancer treatment because it can bind selectively and react with the target diseased sites at the cellular or sub-cellular level, making distribution and release of drugs in a controlled manner, thus enhance therapeutic effects and reduce toxic and side-effects on normal cells. Polyamidoamine dendrimer （PAMAMD） is a kind of newly developed polymer in nanometer degree. Hyper-branched, monodispersity, three-dimensional structure and host-guest entrapment ability make it used as drug carrier, gene delivery system and imaging agent. Various targeting ligands, which have high affinity to specific organs, tissues or cells in human body, can be linked to surface functional groups of PAMAMD. And drugs and theoretical gene are carried by encapsulation or chemical conjugation. Finally, PAMAMD targeting drug delivery system can carry drugs and theoretical gene to diseased sites and then release them for targeted therapy. The PAMAMD-based conjugates have small size, high permeability and retention effect （EPR）, low toxicity and so on. The research progress of PAMAMD modified by different ligands in targeting drug delivery system is reviewed, and research direction of the PAMAMD targeting delivery system in the future is also suggested.