State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
Key Laboratory of Oral Biomedical Research of Zhejiang Province, The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
Small. 2021 Nov;17(47):e2104359. doi: 10.1002/smll.202104359. Epub 2021 Oct 29.
MicroRNAs (miRs) play an important role in regulating gene expression. Limited by their instabilities, miR therapeutics require delivery vehicles. Tetrahedral framework nucleic acids (tFNAs) are potentially applicable to drug delivery because they prominently penetrate tissue and are taken up by cells. However, tFNA-based miR delivery strategies have failed to separate the miRs after they enter cells, affecting miR efficiency. In this study, an RNase H-responsive sequence is applied to connect a sticky-end tFNA (stFNA) and miR-2861, which is a model miR, to target the expression of histone deacetylase 5 (HDAC5) in bone marrow mesenchymal stem cells. The resultant bioswitchable nanocomposite (stFNA-miR) enables efficient miR-2861 unloading and deployment after intracellular delivery, thereby inhibiting the expression of HDAC5 and promoting osteogenic differentiation. stFNA-miR also facilitated ideal bone repair via topical injection. In conclusion, a versatile miR delivery strategy is offered for various biomedical applications that necessitate modulation of gene expression.
微小 RNA（miRs）在调节基因表达方面发挥着重要作用。由于其不稳定性的限制，miR 治疗需要载体。四面体框架核酸（tFNAs）由于能够显著穿透组织并被细胞摄取，因此可能适用于药物递送。然而，基于 tFNA 的 miR 递送策略未能在进入细胞后分离 miR，从而影响 miR 的效率。在这项研究中，应用核糖核酸酶 H 反应序列将粘性末端 tFNA（stFNA）与 miR-2861 连接起来，miR-2861 是一种模型 miR，用于靶向骨髓间充质干细胞中组蛋白去乙酰化酶 5（HDAC5）的表达。所得的生物可切换纳米复合物（stFNA-miR）能够在细胞内递送后有效卸载和部署 miR-2861，从而抑制 HDAC5 的表达并促进成骨分化。stFNA-miR 还通过局部注射促进了理想的骨修复。总之，提供了一种通用的 miR 递送策略，用于需要调节基因表达的各种生物医学应用。
