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材料导报  2019, Vol. 33 Issue (1): 16-26    https://doi.org/10.11896/cldb.201901002
  生物医学工程领域的高技术关键材料 |
微小RNA纳米递送体系的构建及其研究进展
韦晶1, 韩希思1, 张承武1, 吴琼1, 秦晓飞1, 李林1, 余昌敏1, 黄维1,2
1 南京工业大学先进材料研究院,江苏省柔性电子重点实验室,南京 211816
2 西北工业大学陕西柔性电子研究院,西安 710072
Intracellular Delivery of MicroRNA Therapeutics Based on Nanocarriers: Current Status and Future Perspective
WEI Jing1, HAN Xisi1, ZHANG Chengwu1, WU Qiong1, QIN Xiaofei1, LI Lin1, YU Changmin1, HUANG Wei1,2
1 Key Laboratory of Flexible Electronics & Institution of Advanced Materials, Nanjing Tech University (Nanjing Tech), Nanjing 211816
2 Shaanxi Institute of Flexible Electronics, Northwestern Polytechnical University, Xi’an 710072
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摘要 微小RNA是一种短链的、调节性非编码RNA,约由21~25个核苷酸组成,广泛存在动物、植物及病原微生物中,具有在翻译水平调控基因表达的功能,是一类重要的基因表达调节器。目前,已在人类基因组中鉴定出1 000多个miRNA,超过30%的基因受到miRNA调节。miRNA广泛参与细胞生长、分化及凋亡过程。研究表明,生物体内miRNA表达水平与神经障碍、心血管疾病、癌症和病毒感染等疾病密切相关。因此,miRNA已被广泛用作多种疾病的早期诊断、预后评估以及治疗靶点。利用RNA干扰(RNA interference)技术调控生物体内miRNA的含量已经引起越来越多的关注,通过向细胞内递送miRNA或者“反义”核苷酸可以实现对目标miRNA表达水平的调控,从而实现对基因失调所引起的疾病的治疗。目前,基于miRNA的治疗方法在癌症、新发传染病和其他疾病中表现出极大的潜力。然而,核苷酸链自身的特性,如负电性、易降解,导致其很难跨越细胞膜进入细胞。因此,合理设计纳米递送载体,对提高治疗基因的运载和治疗效率具有重要的意义。
   目前,随着新型材料的深入研究,已经报道有多种材料可以作为基因载体并用于细胞内递送miRNA。例如脂质体胶囊,它是利用磷脂双分子层膜所形成的囊泡包裹药物分子而形成的制剂,具有良好的生物相容性和稳定性,可以通过细胞内吞作用进入细胞内,从而实现对基因的递送。此外,利用不同材料的物理、化学特性,多种形式的纳米体系,如聚合物纳米颗粒、有机和无机纳米颗粒等已被开发设计成功能性纳米载体,可实现基因药物的靶向递送和智能刺激释放。本文将讨论细胞内miRNA的功能以及调控miRNA含量的方法,归纳纳米体系在递送miRNA治疗基因方面的研究进展,分析纳米递送体系的设计思路、方法以及作用机制。此外,还将根据目前的研究进展,讨论基于miRNA的疗法在新兴领域中的发展方向,以期为制备新型智能的基因递送体系提供参考。
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韦晶
韩希思
张承武
吴琼
秦晓飞
李林
余昌敏
黄维
关键词:  微小RNA  递送体系  脂质体  聚合物  无机纳米粒子  基因疗法    
Abstract: MicroRNA (miRNA) is a class of small regulatory noncoding RNA (approximately 21—25 bases) endogenously expressed in animals, plants and pathogenic microorganisms. It has the function at the translation level as an important gene expression regulator. Until now, more than 1 000 miRNAs have been identified in organisms, which could regulate around 30% of human genes. MiRNA also plays a key role in cell growth, differentiation and apoptosis. More importantly, studies demonstrate that the expression of miRNAs in organisms is tightly associated with neurological disorders, cardiovascular diseases, cancer and viral infections. Therefore, miRNA has been widely used for early diagnosis, prognostic evaluation and therapeutic targets of many diseases. Regulating expression of miRNA by RNA interference technology in organisms has attracted more and more attention. By delivering miRNA or “antisense” nucleotides to cells, the expression level of target miRNA can be regulated, so as to achieve the treatment of diseases caused by gene disorders. Currently, miRNA-based therapeutics have shown great potential in cancer, emerging infectious diseases and other diseases. However, the characteristics of nucleotide chains, such as negativity and degradability, make it difficult for nucleotide chains to cross cell membranes into cells. Therefore, the rational design of delivery vectors is of great significance for improving the delivery and efficiency of therapeutic genes.
Until now, it has been reported that a variety of materials can be used as gene carriers for intracellular delivery of miRNA. Liposome capsules can enter the cell through endocytosis, which are prepared by encapsulating drug molecules in vesicles formed by phospholipid bilayer membranes. In addition, using the physical and chemical properties of different materials, various forms of nanocarriers, such as polymer nanoparticles, organic and inorganic nanoparticles, have been successfully developed and designed, which can achieve targeted delivery of gene drugs and intelligent stimulus release. In this review, we will discuss the function of intracellular miRNA and the methods of regulating the expression of miRNA, summarize the progress of nanocarriers in delivering miRNA therapeutic genes, and analyze the design ideas, methods and mechanisms of nanocarriers systems. In addition, according to the current research progress, we will discuss the development direction of miRNA-based therapy in emerging areas, in order to provide reference for the preparation of new intelligent gene delivery system.
Key words:  Key words microRNA(miRNA)    delivery system    liposome    polymer    inorganic nanoparticle    gene therapy
               出版日期:  2019-01-10      发布日期:  2019-01-24
ZTFLH:  TM914.4+2  
基金资助: 中央高校杰出青年项目(2017JQ010);国家自然科学基金(61505076);广东省自然科学基金(2017A030313299);江苏省自然科学基金杰出青年基金(BK20170041);制浆造纸工程国家重点实验室开放课题(201706)
作者简介:  韦晶,2017年6月毕业于江苏师范大学,获得工学学士学位。余昌敏,南京工业大学先进材料研究院教授。>黄维,中国科学院院士,俄罗斯科学院外籍院士、名誉博士,西北工业大学常务副校长,教授,博士研究生导师,有机电子学/柔性电子学家, iamcmyu@njtech.edu.cn。
引用本文:    
韦晶, 韩希思, 张承武, 吴琼, 秦晓飞, 李林, 余昌敏, 黄维. 微小RNA纳米递送体系的构建及其研究进展[J]. 材料导报, 2019, 33(1): 16-26.
WEI Jing, HAN Xisi, ZHANG Chengwu, WU Qiong, QIN Xiaofei, LI Lin, YU Changmin, HUANG Wei. Intracellular Delivery of MicroRNA Therapeutics Based on Nanocarriers: Current Status and Future Perspective. Materials Reports, 2019, 33(1): 16-26.
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http://www.mater-rep.com/CN/10.11896/cldb.201901002  或          http://www.mater-rep.com/CN/Y2019/V33/I1/16
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