@article{c583376e814f49ea98eb30c9cc895d31,
title = "Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy",
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.",
author = "Chao Liang and Baosheng Guo and Heng Wu and Ningsheng Shao and Defang Li and Jin Liu and Lei Dang and Cheng Wang and Hui Li and Shaohua Li and Lau, {Wing Ki} and Yu Cao and Zhijun Yang and Cheng Lu and Xiaojuan He and Au, {D. W.T.} and Xiaohua Pan and Zhang, {Bao Ting} and Changwei Lu and Zhang, {Hong Qi} and Yue, {Kevin K M} and Airong Qian and Peng Shang and Jiake Xu and Lianbo Xiao and Zhaoxiang Bian and Weihong Tan and Zicai Liang and Fuchu He and Lingqiang Zhang and Aiping Lu and Ge Zhang",
note = "We thank the academic staff (L. Qin) from the Chinese University of Hong Kong and H.Y.S. Cheung from the Institute for Advancing Translational Medicine in Bone & Joint Diseases, Hong Kong Baptist University for providing critical comments and technical support. This study was supported by the Ministry of Science and Technology of China (2013ZX09301307 to A.L.), the Hong Kong General Research Fund (HKBU479111 to G.Z., HKBU478312 to G.Z., HKBU12102914 to G.Z. and HKBU261113 to A.L.), the Natural Science Foundation Council of China (81272045 to G.Z., 81228013 to J.X. and 21221003 to W.T.), the Research Grants Council & Natural Science Foundation Council of China (N_HKBU435/12 to G.Z.), the Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/12-13/02 to A.L. and RC-IRMS/13-14/02 to G.Z.), the Hong Kong Baptist University Strategic Development Fund (SDF) (SDF13-1209-P01 to A.L.), the Hong Kong Research Grants Council (RGC) Early Career Scheme (ECS) (489213 to B.-T.Z.), the Faculty Research Grant of Hong Kong Baptist University (FRG1/13-14/024 and FRG2/12-13/027 to G.Z.), the China Academy of Chinese Medical Sciences (Z0252 and Z0293 to A.L.), the Chinese National High-Tech Research and Development Programme (2012AA022501 to N.S.), the National Key Technologies R&D Programs for New Drugs of China (2012ZX09301003-001-001 and 2014ZX09J14106-04C to L.Z.), the Collaborative Research Programme (CRP)-International Centre for Genetic Engineering and Biotechnology (ICGEB) grant (CRP/CHN13-02 to L.Z.), the Chinese National Natural Science Foundation Project (81261160503 to L.Z.), the National Key Scientific Program of China (2011CB911000 to W.T.), the National Institutes of Health (GM079359 to W.T.) and the Beijing Natural Science Foundation (7131012 to L.Z.). The statistical analysis was performed by a contract service from Bioinformedicine.",
year = "2015",
month = mar,
doi = "10.1038/nm.3791",
language = "English",
volume = "21",
pages = "288--294",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "3",
}
