作者
Chao Liang,Baosheng Guo,Heng Wu,Ningsheng Shao,Defang Li,Jin Liu,Lei Dang,Wang Cheng,Hui Li,Shaohua Li,Wing Ki Lau,Ya Cao,Zhijun Yang,Cheng Lü,Xiaojuan He,Doris W.T. Au,Xiaohua Pan,Bao-Ting Zhang,Changwei Lu,Hongqi Zhang,Kevin K M Yue,Airong Qian,Peng Shang,Jiake Xu,Lianbo Xiao,Zhaoxiang Bian,Tan Wang,Zicai Liang,Fuchu He,Lingqiang Zhang,Aiping Lü,Ge Zhang
摘要
Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer-functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.