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Liang, Chao; Guo, Baosheng; Wu, Heng; Shao, Ningsheng; Li, Defang; Liu, Jin; Dang, Lei; Wang, Cheng; Li, Hui; Li, Shaohua; Lau, Wing Ki; Cao, Yu; Yang, Zhijun; Lu, Cheng; He, Xiaojuan; Au, D W T; Pan, Xiaohua; Zhang, Bao-Ting; Lu, Changwei; Zhang, Hongqi; Yue, Kinman; Qian, Airong; Shang, Peng; Xu, Jiake; Xiao, Lianbo; Bian, Zhaoxiang; Tan, Weihong; Liang, Zicai; He, Fuchu; Zhang, Lingqiang; Lu, Aiping; Zhang, Ge
Nature medicine, 03/2015, Volume: 21, Issue: 3Journal Article
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.
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