摘要
纳米载体由于增强渗透阻滞(EPR)效应可以高效富集于肿瘤部位,有利于增强药物体内循环时间和增强药物稳定性,从而成为增强肿瘤治疗和诊断效果的有力手段。作为一种天然来源的生物大分子,多糖具有良好的生物相容性和生物功能性,可以实现主动靶向,如透明质酸具有特异性靶向到CD44受体的功能。因此由多糖制备的纳米载体是抗肿瘤药物包封和靶向控释的优异候选材料之一。目前葡聚糖、壳聚糖、透明质酸及海藻酸盐等多种多糖已成功用于多糖纳米载体的制备及相关生物医学应用。在包括乳化、自组装等制备多糖纳米载体的不同方法中,自组装途径由于其适用范围广、所得载体性能可控,已成为多糖纳米载体制备的主要方式。多糖纳米载体的自组装途径主要包括聚电解质吸附自组装、基于多糖聚合物的两步法自组装、以及聚合/自组装联合的一步法途径。目前来说,制备多糖纳米载体多通过先进行多糖改性或多糖共聚物合成、进而由不同的驱动力诱导多糖共聚物自组装这两步骤完成。但总体上,较为复杂的多糖改性方法、以及多糖溶液自组装中较低的固含量都造成两步法制备多糖纳米载体时效率较低,难以满足实际应用的需求。近年来,包括我们在内的一些研究组提出通过"聚合-自组装"二合一的途径实施多糖纳米载体的"一步法"制备。即从多糖出发,在单体于多糖主链上的接枝共聚过程中,驱动共聚物的溶液相自组装,从而一步制得多糖基纳米载体。在"一步法"途径中,纳米载体的制备效率得以显著提升,并可通过引入适当的功能性单体赋予纳米载体以特定的功能性。这一途径为多糖纳米载体的制备提供了新的思路。本文主要从多糖纳米载体制备的自组装途径出发,分类介绍了由不同自组装驱动力制备多糖纳米载体的方法,在对"两步法"制备多糖纳米载体的驱动力进行归纳的基础上,着重介绍接枝共聚诱导自组装的"一步法"途径。此外,基于多糖本身特殊的生物功能性,如细胞识别等特点,本文还介绍了多糖纳米载体的主动靶向药物输运等生物应用,以期能为高效制备具有生物功能性的多糖纳米载体提供借鉴。
Nano carriers,due to the enhanced osmotic blockade(EPR)effect,can highly enrich in the tumor site,which is conducive to enhancing the internal circulation time and drug stability,and thus become a powerful means to enhance the therapeutic and diagnostic effect of tumor.As a natural biological macromolecule,polysaccharide has good biocompatibility and biological function,which can achieve active targeting.For example,hyaluronic acid has the function of specific targeting to CD44 receptor.Therefore,the nano carrier prepared from polysaccharide is one of the excellent candidate materials for anticancer drug encapsulation and targeted controlled release.At present,dextran,chitosan,hyaluronic acid,alginate and other polysaccharides have been successfully used in the preparation of polysaccharide nano carriers and related biomedical applications.Among the different methods of preparing polysaccharide nano carriers,including emulsification and self-assembly,self-assembly has become the main way of preparing polysaccharide nano carriers because of its wide application and controllable performance.The self-assembly of polysaccharide nano carriers mainly includes polyelectrolyte adsorption self-assembly,two-step self-assembly based on polysaccharide polymer,and one-step polymerization/self-assembly.At present,the preparation of polysaccharide nano carriers is mainly through two steps:first,the modification of polysaccharide or the synthesis of polysaccharide copolymers,and then the self-assembly of polysaccharide copolymers induced by different driving forces.However,the complex modification methods of polysaccharides and the low solid content in the self-assembly of polysaccharide solution result in the low aging rate of the two-step preparation of polysaccharide nano carriers,which is difficult to meet the needs of practical application.In recent years,some research groups including us have proposed the"one-step"preparation of polysaccharide nano carriers by the"polymerization self-assembly"two in one way.From the point of view of polysaccharides,in the process of grafting copolymerization of monomers on the main chain of polysaccharides,the solution phase self-assembly of the copolymers is driven,and then the nano carrier of polysaccharide group is prepared in one step.In the"one-step"approach,the preparation efficiency of nano carriers can be significantly improved,and the nano carriers can be given specific functionality by introducing appropriate functional monomers.This approach provides a new way for the preparation of polysaccharide nano carriers.In this paper,the self-assembly methods for the preparation of polysaccharide nano carriers are introduced.Based on the induction of the driving force for the preparation of polysaccharide nano carriers by"two-step"method,the"one-step"method for the self-assembly induced by graft copolymerization is emphasized.In addition,based on the special biological functions of polysaccharides,such as cell recognition,this paper also introduces the active target drug transport and other biological applications of polysaccharide nano carriers,in order to provide reference for the efficient preparation of polysaccharide nano carriers with biological functions.
作者
黄晚秋
高苗苗
徐源
窦红静
HUANG Wan-qiu;GAO Miao-miao;XU Yuan;DOU Hong-jing(State Key Laboratory of Metal Matrix Composites,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai 200240,China)
出处
《高分子通报》
CAS
CSCD
北大核心
2020年第10期21-29,共9页
Polymer Bulletin
基金
国家自然科学基金(21871180)
上海市“科技创新行动计划”基础研究领域项目(18JC1413500)
上海高校特聘教授(东方学者)计划(SHDP201802)
上海市教委“曙光计划”(12SG12)资助
关键词
多糖纳米载体
自组装途径
两步法
一步法
主动靶向
Polysaccharide nanocarrier
Self-assembly approach
Two-step method
One-step method
Active targeting
