Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications

被引:22
作者
Asakiya, Charles [1 ,2 ]
Zhu, Liye [1 ,2 ]
Yuhan, Jieyu [1 ,2 ]
Zhu, Longjiao [2 ]
Huang, Kunlun [2 ]
Xu, Wentao [1 ,2 ]
机构
[1] China Agr Univ, Dept Nutr & Hlth, Key Lab Precis Nutr & Food Qual, Beijing, Peoples R China
[2] China Agr Univ, Coll Food Sci & Nutr Engn, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
MiRNA-derivative nucleotide drugs; application; modifications; delivery systems; stimuli-responsive system; MICRORNA DELIVERY; GOLD NANOPARTICLE; CO-DELIVERY; CANCER; THERAPEUTICS; DOXORUBICIN; EFFICIENT; LIPOSOME; MIR-34A; OXIDE;
D O I
10.1080/17425247.2022.2063835
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: miRNA-derivative clinical nucleotide drugs (mdCNDs) effectively treat several diseases, with numerous undergoing clinical trials. In early-stage trials in disease therapeutics, such as malignant pleural mesothelioma and hepatic virus C infection, mdCND's therapeutic potency is undeniably good for effectiveness and safety. Areas covered: Fifteen mdCNDs undergoing clinical trials are introduced in this review. MiRNA modifications methods have been summarized, including phosphorothioate, cholesterol, locked nucleic acid, 2'-O-methyl, N,N-diethyl-4-(4-nitronaphthalen1-ylazo)-phenylamine modifications, and many more. Moreover, delivery systems, including self-assembled, inorganic ions nanoparticles, exosomes, and lipid-based nanosystems for mdCNDs targeted delivery, are presented. Among that, EnGeneIC, N-Acetylgalactosamine, liposomal nanoparticles, and cholesterol-conjugated for mdCNDs delivery are currently undergoing clinical trials. The pH, light, temperature, redox-responsive, enzyme, and specificsubstance modes to trigger the release of miRNAs to target sites on-demand and the prospects of mdCNDs are discussed in this review. Expert opinion: mdNCDs are one type of promising clinical drugs, however, it is still in the infancy. During the development process, it is imperative to advance in modifying miRNAs, especially at the 5'end, to enhance targetability and stability against nucleases, develop a stimuli-responsive mode to control the release of mdCNDs to tissue cell-type-specific sites. [GRAPHICS]
引用
收藏
页码:435 / 450
页数:16
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