Bioswitchable Delivery of microRNA by Framework Nucleic Acids: Application to Bone Regeneration

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 17; no. 47; pp. e2104359 - n/a
• Main Authors: Li, Songhang, Liu, Yuhao, Tian, Taoran, Zhang, Tao, Lin, Shiyu, Zhou, Mi, Zhang, Xiaolin, Lin, Yunfeng, Cai, Xiaoxiao
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2021
• Subjects: Biomedical materials; Bone marrow; Bone Regeneration; Cell Differentiation; Differentiation (biology); DNA nanotechnology; drug delivery; framework nucleic acid; Gene expression; Mesenchymal Stem Cells; microRNA; MicroRNAs; Nanocomposites; Nanotechnology; Nucleic Acids; Osteogenesis; Regeneration (physiology); Ribonucleic acid; RNA; Stem cells; DNA nanotechnology; bone regeneration; microRNA; drug delivery; framework nucleic acid
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202104359

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. Due to their instabilities, miR therapeutics require delivery vehicles. Herein, an RNase H‐responsive sequence is applied to connect sticky‐end tFNA and miR, enabling efficient unloading and deployment of miR‐2861 after intracellular delivery. The bioswitchable nanocomposite promotes in vitro osteogenic differentiation and in vivo bone regeneration, and is potentially applicable to other biomedical fields such as tumor targeting.