賀香港浸會大學(xué)等應(yīng)用PriCells產(chǎn)品/技術(shù)服務(wù)發(fā)表文章
Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference–based bone anabolic strategy
Nature Medicine (2015) doi:10.1038/nm.3791
Received 06 February 2014 Accepted 02 December 2014 Published online 09 February 2015
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, D W T Au, Xiaohua Pan, Bao-Ting Zhang, Changwei Lu, Hongqi Zhang, Kinman Yue, Airong Qian, Peng Shang, Jiake Xu, Lianbo Xiao,et al.
11] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China. [4] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [5] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [7] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [8] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China,et al
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.
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