| Literature DB >> 25665179 |
Chao Liang1, Baosheng Guo2, Heng Wu3, Ningsheng Shao4, Defang Li5, Jin Liu5, Lei Dang5, Cheng Wang6, Hui Li4, Shaohua Li4, Wing Ki Lau7, Yu Cao8, Zhijun Yang3, Cheng Lu2, Xiaojuan He9, D W T Au10, Xiaohua Pan7, Bao-Ting Zhang11, Changwei Lu7, Hongqi Zhang7, Kinman Yue7, Airong Qian12, Peng Shang12, Jiake Xu13, Lianbo Xiao14, Zhaoxiang Bian3, Weihong Tan15, Zicai Liang16, Fuchu He8, Lingqiang Zhang8, Aiping Lu17, Ge Zhang18.
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.Entities:
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Year: 2015 PMID： 25665179 PMCID： PMC5508976 DOI： 10.1038/nm.3791
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440