基于纳米材料的CpG核酸药物载运系统  

CpG ODN delivery systems based on nanomaterials

作　　者：魏敏[1] 李江[1] 陈楠[1] 黄庆[1] 樊春海[1] 

机构地区：[1]中国科学院上海应用物理研究所物理生物学实验室,上海201800

出　　处：《科学通报》2014年第2期133-145,共13页Chinese Science Bulletin

基　　金：国家自然科学基金重大研究计划(90913014)资助

摘　　要：人工合成的含有胞嘧啶-鸟嘌呤二核苷酸的脱氧寡核苷酸(CpG ODN)可以模拟细菌DNA的免疫激活作用,被哺乳动物免疫系统视为"危险"信号而引发机体产生免疫应答.因此,CpG ODN可以作为潜在的治疗性DNA和免疫佐剂,在感染性疾病、过敏性疾病和癌症的辅助治疗中发挥作用.然而,未经修饰的CpG ODN通常易被核酸酶降解,细胞摄取率低,需要较高的给药剂量和反复给药,这些缺陷严重地限制了CpG的应用.近年来,纳米技术的发展为解决核酸药物的递送问题提供了新的工具.已有大量研究报道显示,纳米材料负载的CpG核酸药物表现出高活性、低毒性、生物相容性好等特点,有望作为新型免疫治疗制剂应用于相关疾病的预防和治疗中.本文对CpG核酸药物的发展背景进行了简述,介绍了CpG药物的作用机制、CpG载运对载体材料提出的要求,重点对近年来兴起的多种基于新型纳米材料(包括纳米脂质体/共聚物、各种无机纳米材料和DNA纳米结构等)的CpG载运体系进行了评述,总结了各种载运系统的原理和特点,并对纳米材料递送CpG药物的发展趋势进行了展望.Artificially synthesized CpG oligodeoxynucleotides （CpG ODNs） can imitate bacterial DNA and effectively stimulate the mammalian immune system in response to signals resulting from hazardous invasion. For this reason, CpG ODNs represent promising materials with a range of applications in the treatment of different infections, allergies and cancers. Unfortunately, however, unmodified CpG ODNs alone can be readily degraded by enzymes, resulting in a reduced level of uptake into cells. Repeated high-dose drug administration is therefore required in these treatments, which largely limits their application. In recent years, significant progress in nanomaterial technology has provided a range of new opportunities for the development of effective delivery systems for nucleotide drugs. Based on reports from the literature, a variety of different nanomaterial-based CpG delivery systems have been developed that show a range of advantages, such as high levels of activity, low toxicity and good biocompatibility, making them excellent candidates for use in therapeutic reagents in immune-related diseases. Herein, we provide an introduction to the background and development history of CpG ODN drugs, including their mechanisms of action and the requirements for successful delivery. Particular emphasis has been given to newly developed CpG delivery systems based on different nanomaterials, with a summary of their respective principles and features. Furthermore, we have provided a sketch of the prospects and future trends expected of these materials.

关 键 词：CPG 纳米载体 药物载运 DNA纳米结构 

分 类 号：TQ460.1[化学工程—制药化工]