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用于增强CpG寡脱氧核苷酸免疫刺激作用的纳米递送系统。

Nanodelivery systems for enhancing the immunostimulatory effect of CpG oligodeoxynucleotides.

作者信息

Zhang Huijie, Gao Xiao-Dong

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Jan 1;70(Pt 2):935-946. doi: 10.1016/j.msec.2016.03.045. Epub 2016 Mar 16.

Abstract

Synthetic oligodeoxynucleotides containing immunostimulatory CpG motif mimic bacterial DNA and are potent activator of innate and adaptive immune responses. Therefore, CpG ODNs have significant potentials as immunotherapeutic agent for treatment of infectious diseases, allergy and cancer. Many clinical trials involving CpG ODNs either used alone or as adjuvant have been initiated. However, delivery of CpG ODNs to target sites still remains a great challenge due to their extreme susceptibility to nuclease degradation in serum and poor cellular uptake. Chemical modification of CpG ODNs backbone can protect them against degradation by nucleases, but have raised concern regarding several severe side effects. Development of efficient CpG ODNs delivery systems to address these issues and enhance their immunostimulatory effect are highly desirable. In recent years, the emergence of nanotechnology has provided unprecedented opportunities to encapsulate CpG ODN into various nanocarriers or synthesize CpG ODNs nanostructures. This review provides an overview of the delivery systems based on nanomaterials and nanostructures newly developed for enhancing the immunostimulatory effect of CpG ODNs, together with a brief discussion on perspectives for future studies in this field.

摘要

含有免疫刺激CpG基序的合成寡脱氧核苷酸模拟细菌DNA,是先天免疫和适应性免疫反应的有效激活剂。因此,CpG寡脱氧核苷酸作为治疗传染病、过敏和癌症的免疫治疗剂具有巨大潜力。许多涉及单独使用或作为佐剂使用CpG寡脱氧核苷酸的临床试验已经启动。然而,由于CpG寡脱氧核苷酸在血清中极易被核酸酶降解且细胞摄取能力差,将其递送至靶位点仍然是一个巨大的挑战。对CpG寡脱氧核苷酸骨架进行化学修饰可以保护它们不被核酸酶降解,但引发了对几种严重副作用的担忧。开发高效的CpG寡脱氧核苷酸递送系统以解决这些问题并增强其免疫刺激作用是非常必要的。近年来,纳米技术的出现为将CpG寡脱氧核苷酸封装到各种纳米载体中或合成CpG寡脱氧核苷酸纳米结构提供了前所未有的机会。本文综述了基于纳米材料和纳米结构新开发的用于增强CpG寡脱氧核苷酸免疫刺激作用的递送系统,并简要讨论了该领域未来研究的前景。

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