Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Chao Liang
  • Baosheng Guo
  • Heng Wu
  • Ningsheng Shao
  • Defang Li
  • Jin Liu
  • Lei Dang
  • Cheng Wang
  • Hui Li
  • Shaohua Li
  • Wing Ki Lau
  • Yu Cao
  • Zhijun Yang
  • Cheng Lu
  • Xiaojuan He
  • Xiaohua Pan
  • Bao-Ting Zhang
  • Changwei Lu
  • Hongqi Zhang
  • Kinman Yue
  • Airong Qian
  • Peng Shang
  • Jiake Xu
  • Lianbo Xiao
  • Zhaoxiang Bian
  • Weihong Tan
  • Zicai Liang
  • Fuchu He
  • Lingqiang Zhang
  • Aiping Lu
  • Ge Zhang

Detail(s)

Original languageEnglish
Pages (from-to)288-294
Journal / PublicationNature Medicine
Volume21
Issue number3
Online published9 Feb 2015
Publication statusPublished - Mar 2015

Abstract

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.

Citation Format(s)

Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. / 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.

In: Nature Medicine, Vol. 21, No. 3, 03.2015, p. 288-294.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review