文章信息/Info

Title:

Telodendrimers for the delivery of therapeutic proteins

作者:

鐘淵博; 王 旭

山東大學(xué) 國家膠體材料工程技術(shù)研究中心

Author(s):

ZHONG Yuanbo;  WANG Xu

National Engineering Research Center for Colloidal Materials, Shandong University

關(guān)鍵詞:

線性-樹枝狀嵌段共聚物; 納米粒子; 蛋白質(zhì)封裝; 靶向遞送; 胞內(nèi)傳遞; 疾病治療

Keywords:

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

DOI:

10.7502/j.issn.1674-3962.2018.04.04

文獻(xiàn)標(biāo)志碼:

A

摘要:

線性-樹枝狀嵌段共聚物(telodendrimer)是由線性高分子與樹枝狀嵌段通過化學(xué)鍵連接而成的一類特殊拓?fù)浣Y(jié)構(gòu)的共聚物。這類共聚物具有高度可調(diào)的化學(xué)組成及結(jié)構(gòu)，其可根據(jù)需求設(shè)計(jì)成為與蛋白質(zhì)藥物具有多重雜化超分子相互作用力的大分子，以用于蛋白質(zhì)藥物的穩(wěn)定封裝及靶向輸送。線性-樹枝狀嵌段共聚物作為一種理想的蛋白質(zhì)藥物載體，可實(shí)現(xiàn)以下四個(gè)方面的功能：(1)其可有效封裝蛋白質(zhì)分子從而形成尺寸在30納米以下的納米粒子，并通過被動靶向作用將蛋白質(zhì)運(yùn)送至腫瘤部位；(2)其可與類脂質(zhì)(lipidoid)形成復(fù)合納米粒子用于截短型白喉毒素(DT390)的細(xì)胞內(nèi)傳遞及原位腦瘤的有效治療；(3)其可結(jié)合計(jì)算機(jī)虛擬篩選技術(shù)從而根據(jù)蛋白質(zhì)藥物的結(jié)構(gòu)進(jìn)行聚合物納米載體的定制化設(shè)計(jì)，并應(yīng)用于胰島素的遞送進(jìn)而實(shí)現(xiàn)對血糖值的有效控制；(4)其還可作為可移除型保護(hù)層與陽離子聚合物復(fù)合，在有效進(jìn)行蛋白質(zhì)胞內(nèi)傳遞的同時(shí)降低陽離子聚合物引起的細(xì)胞毒性、溶血性及非特異性吸附或聚集。本文總結(jié)了基于線性-樹枝狀嵌段共聚物的蛋白質(zhì)藥物遞送系統(tǒng)的研究進(jìn)展，并討論了其對疾病的治療情況。

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.