用于递送微小RNA的聚合物纳米载体
Polymer nanocarriers for MicroRNA delivery.
作者信息
Kapadia Chintan H, Luo Benjamin, Dang Megan N, Irvin-Choy N'Dea, Valcourt Danielle M, Day Emily S
机构信息
Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19716.
Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716.
出版信息
J Appl Polym Sci. 2020 Jul 5;137(25). doi: 10.1002/app.48651. Epub 2019 Nov 12.
Abnormal expression of microRNAs (miRNAs), which are highlyconserved noncoding RNAs that regulate the expression of various genes post transcriptionally to control cellular functions, has been associated with the development of many diseases. In some cases, disease-promoting miRNAs are upregulated, while in other instances disease-suppressive miRNAs are downregulated. To alleviate this imbalanced miRNA expression, either antagomiRs or miRNA mimics can be delivered to cells to inhibit or promote miRNA expression, respectively. Unfortunately, the clinical translation of bare antagomiRs and miRNA mimics has been challenging because nucleic acids are susceptible to nuclease degradation, display unfavorable pharmacokinetics, and cannot passively enter cells. This review emphasizes the challenges associated with miRNA mimic delivery and then discusses the design and implementation of polymer nanocarriers to overcome these challenges. Preclinical efforts are summarized, and a forward-looking perspective on the future clinical translation of polymer nanomaterials as miRNA delivery vehicles is provided.
微小RNA（miRNA）的异常表达与多种疾病的发生发展相关。miRNA是高度保守的非编码RNA，可在转录后调控各种基因的表达以控制细胞功能。在某些情况下，促疾病的miRNA会上调，而在其他情况下，抑疾病的miRNA会下调。为了缓解这种miRNA表达失衡的情况，可以分别将抗miR或miRNA模拟物导入细胞以抑制或促进miRNA表达。不幸的是，单纯的抗miR和miRNA模拟物的临床转化一直具有挑战性，因为核酸易受核酸酶降解，具有不良的药代动力学，且不能被动进入细胞。本文综述强调了与miRNA模拟物递送相关的挑战，然后讨论了聚合物纳米载体的设计与应用以克服这些挑战。总结了临床前的研究工作，并对聚合物纳米材料作为miRNA递送载体的未来临床转化提供了前瞻性展望。
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