线性-树枝状嵌段共聚物用于蛋白质药物的递送-中国材料进展

文章信息/Info

Author(s):: ZHONG Yuanbo; WANG Xu; National Engineering Research Center for Colloidal Materials, Shandong University

Keywords:: telodendrimer; nanoparticles; protein encapsulation; targeted delivery; intracellular delivery; disease treatment

摘要:: 线性-树枝状嵌段共聚物(telodendrimer)是由线性高分子与树枝状嵌段通过化学键连接而成的一类特殊拓扑结构的共聚物。这类共聚物具有高度可调的化学组成及结构，其可根据需求设计成为与蛋白质药物具有多重杂化超分子相互作用力的大分子，以用于蛋白质药物的稳定封装及靶向输送。线性-树枝状嵌段共聚物作为一种理想的蛋白质药物载体，可实现以下四个方面的功能：(1)其可有效封装蛋白质分子从而形成尺寸在30纳米以下的纳米粒子，并通过被动靶向作用将蛋白质运送至肿瘤部位；(2)其可与类脂质(lipidoid)形成复合纳米粒子用于截短型白喉毒素(DT390)的细胞内传递及原位脑瘤的有效治疗；(3)其可结合计算机虚拟筛选技术从而根据蛋白质药物的结构进行聚合物纳米载体的定制化设计，并应用于胰岛素的递送进而实现对血糖值的有效控制；(4)其还可作为可移除型保护层与阳离子聚合物复合，在有效进行蛋白质胞内传递的同时降低阳离子聚合物引起的细胞毒性、溶血性及非特异性吸附或聚集。本文总结了基于线性-树枝状嵌段共聚物的蛋白质药物递送系统的研究进展，并讨论了其对疾病的治疗情况。

Abstract:: Telodendrimer specifically refers to a linear-dendritic copolymer containing a single monodendron or dendrimer and a linear segment attached at the “focal” point of the dendritic fragment. The well-defined chemical structure of telodendrimer allows for precise engineering of functionalities in telodendrimer for stable incorporation of therapeutic proteins via multivalent and hybrid interactions. The telodendrimer provides a versatile platform that enables (i) the encapsulation of proteins to form nanoparticles for tumor-targeted protein delivery by the enhanced permeability and retention effects, (ii) the formation of lipidoid-telodendrimer hybrid nanoparticles for intracellular delivery of truncated diphtheria toxin in brain tumor treatment, (iii) the structure-based nanocarrier design for insulin delivery towards effective control of blood glucose levels, and (iv) the detachable protection of protein-polycation nanocomplex for efficient intracellular protein delivery with reduced polycation-associated cytotoxicity and hemolytic activity, as well as eliminated aggregation and non-specific binding of polycations to other biomacromolecules. In this review, the telodendrimer-based protein delivery systems are summarized. The affinity-controlled protein encapsulation and the targeted and/or intracellular protein delivery for disease treatments by employing telodendrimer nanocarriers are discussed.