A Tetrahedral Framework DNA‐Based Bioswitchable miRNA Inhibitor Delivery System: Application to Skin Anti‐Aging. Issue 46 (28th July 2022)

• Record Type: Journal Article
• Authors: Li, Songhang; Liu, Yuhao; Zhang, Tao; Lin, Shiyu; Shi, Sirong; He, Jiajun; Xie, Yu; Cai, Xiaoxiao; Tian, Taoran; Lin, Yunfeng
• Is Part Of: Advanced materials. Volume 34:Issue 46(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-28
• Subjects: aging -- DNA nanotechnology -- drug delivery -- framework nucleic acid -- microRNAs; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202204287
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: MicroRNA (miR)‐based therapy shows strong potential; however, structural limitations pose a challenge in fully exploiting its biomedical functionality. Tetrahedral framework DNA (tFNA) has proven to be an ideal vehicle for miR therapy. Inspired by the ancient Chinese myth "Sun and Immortal Birds, " a novel bioswitchable miR inhibitor delivery system (BiRDS) is designed with three miR inhibitors (the three immortal birds) and a nucleic acid core (the central sun). The BiRDS fuses miR inhibitors within the framework, maximizing their loading capacity, while allowing the system to retain the characteristics of small‐sized tFNA and avoiding uncertainty associated with RNA exposure in traditional loading protocols. The RNase H‐responsive sequence at the tail of each "immortal bird" enables the BiRDS to transform from a 3D to a 2D structure upon entering cells, promoting the delivery of miR inhibitors. To confirm the application potential, the BiRDS is used to deliver the miR‐31 inhibitor, with antiaging effects on hair follicle stem cells, into a skin aging model. Superior skin penetration ability and RNA delivery are observed with significant anti‐aging effects. These findings demonstrate the capability and editability of the BiRDS to improve the stability and delivery efficacy of miRs for future innovations. Abstract : A bioswitchable miR inhibitor delivery system (BiRDS) is designed. BiRDS maximizes miR inhibitors' loading capacity while retaining the characteristics of small‐sized tFNA. Superior skin penetration ability and RNA delivery are observed with significant anti‐aging effects. The excellent editability of the BiRDS confers it the potential to significantly improve the stability and delivery efficiency of miR inhibitors.