Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference–based…

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


Liang C, Guo B, Wu H, Shao N, Li D, Liu J, Dang L, Wang C, Li H, Li S, Lau WK, Cao Y, Yang Z, Lu C, He X, Au DW, Pan X, Zhang BT, Lu C, Zhang H, Yue K, Qian A, Shang P, Xu J, Xiao L, Bian Z, Tan W, Liang Z, He F, Zhang L, Lu A, Zhang G

Nat Med. 2015 Mar;21(3):288-94. doi: 10.1038/nm.3791.

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.