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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03

AUTHORS

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, Zhaoxiang Bian, Weihong Tan, Zicai Liang, Fuchu He, Lingqiang Zhang, Aiping Lu, Ge Zhang

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. More... »

PAGES

288-294

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.3791

DOI

http://dx.doi.org/10.1038/nm.3791

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033882648

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25665179


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