A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids:Application to endogenous regeneration of articular cartilage  

作　　者：Liwei Fu Jiang Wu Pinxue Li Yazhe Zheng Zhichao Zhang Xun Yuan Zhengang Ding Chao Ning Xiang Sui Shuyun Liu Sirong Shi Quanyi Guo Yunfeng Lin 

机构地区：[1]School of Medicine,Nankai University,Tianjin,300071,People’s Republic of China [2]Institute of Orthopedics,The First Medical Center,Chinese PLA General Hospital,Beijing Key Lab of Regenerative Medicine in Orthopedics,Key Laboratory of Musculoskeletal Trauma&War Injuries PLA,No.28 Fuxing Road,Haidian District,Beijing,People’s Republic of China [3]Department of Orthopedics,The Fourth Medical Center,Chinese PLA General Hospital,Beijing,People’s Republic of China [4]National Clinical Research Center for Orthopedics,Sports Medicine&Rehabilitation,Beijing,People’s Republic of China [5]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,People’s Republic of China [6]Guizhou Medical University,Guiyang,550004,Guizhou Province,People’s Republic of China

出　　处：《Bioactive Materials》2024年第10期634-648,共15页生物活性材料（英文）

基　　金：supported by the Natural Science Foundation of Beijing Municipality(L234024)。

摘　　要：Articular cartilage injury(ACI)remains one of the key challenges in regenerative medicine,as current treatment strategies do not result in ideal regeneration of hyaline-like cartilage.Enhancing endogenous repair via micro-RNAs(miRNAs)shows promise as a regenerative therapy.miRNA-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells(MSCs).In this study,we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid(tFNA)-based targeting miRNA codelivery system,named A-T-M,was used.With tFNAs as vehicles,miR-140 and miR-455 were connected to and modified on tFNAs,while Apt19S(a DNA aptamer targeting MSCs)was directly integrated into the nanocomplex.The relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding mechanisms.Interestingly,a synergistic effect between miR-140 and miR-455 was revealed.Furthermore,A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation.A-T-M provides a new perspective and strategy for the regeneration of articular cartilage,showing strong clinical application value in the future treatment of ACI.

关 键 词：Tetrahedral framework nucleic acids miRNAs co-delivery Targeting system Articular cartilage endogenous regeneration Mesenchymal stem cells 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]