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

香港中文大學研究人員

引用次數
替代計量分析
.

其它資訊
摘要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.
著者Liang C, Guo BS, Wu H, Shao NS, Li DF, Liu J, Dang L, Wang C, Li H, Li SH, Lau WK, Cao Y, Yang ZJ, Lu C, He XJ, Au DWT, Pan XH, Zhang BT, Lu CW, Zhang HQ, Yue KM, Qian AR, Shang P, Xu JK, Xiao LB, Bian ZX, Tan WH, Liang ZC, He FC, Zhang LQ, Lu AP, Zhang G
期刊名稱Nature Medicine
出版年份2015
月份3
日期1
卷號21
期次3
出版社Nature Publishing Group
頁次288 - +
國際標準期刊號1078-8956
電子國際標準期刊號1546-170X
語言英式英語
Web of Science 學科類別Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Research & Experimental Medicine

上次更新時間 2020-16-09 於 00:29