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

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

doi:10.1038/nm.3791

Author(s)

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
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

Detail(s)

Original language	English
Pages (from-to)	288-294
Journal / Publication	Nature Medicine
Volume	21
Issue number	3
Online published	9 Feb 2015
Publication status	Published - Mar 2015

Link(s)

DOI	DOI https://doi.org/10.1038/nm.3791 Final Published version
	Check@CityULib
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-84925516251&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(935e40ac-e71d-45ef-bdc6-fcd6617dc4fe).html

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.

Citation Format(s)

[ RIS ] [ BibTeX ]

Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. / Liang, Chao; Guo, Baosheng; Wu, Heng; Shao, Ningsheng; Li, Defang; Liu, Jin; Dang, Lei; Wang, Cheng; Li, Hui; Li, Shaohua; Lau, Wing Ki; Cao, Yu; Yang, Zhijun; Lu, Cheng; He, Xiaojuan; Au, D. W T; Pan, Xiaohua; Zhang, Bao-Ting; Lu, Changwei; Zhang, Hongqi; Yue, Kinman; Qian, Airong; Shang, Peng; Xu, Jiake; Xiao, Lianbo; Bian, Zhaoxiang; Tan, Weihong; Liang, Zicai; He, Fuchu; Zhang, Lingqiang; Lu, Aiping; Zhang, Ge.

In: Nature Medicine, Vol. 21, No. 3, 03.2015, p. 288-294.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review

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, DWT, Pan, X, Zhang, B-T, 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 2015, 'Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy', Nature Medicine, vol. 21, no. 3, pp. 288-294. https://doi.org/10.1038/nm.3791

Liang, C., Guo, B., Wu, H., Shao, N., Li, D., Liu, J., Dang, L., Wang, C., Li, H., Li, S., Lau, W. K., Cao, Y., Yang, Z., Lu, C., He, X., Au, D. W. T., Pan, X., Zhang, B-T., Lu, C., ... Zhang, G. (2015). Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nature Medicine, 21(3), 288-294. https://doi.org/10.1038/nm.3791

Liang C, Guo B, Wu H, Shao N, Li D, Liu J et al. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nature Medicine. 2015 Mar;21(3):288-294. https://doi.org/10.1038/nm.3791

Liang, Chao ; Guo, Baosheng ; Wu, Heng ; Shao, Ningsheng ; Li, Defang ; Liu, Jin ; Dang, Lei ; Wang, Cheng ; Li, Hui ; Li, Shaohua ; Lau, Wing Ki ; Cao, Yu ; Yang, Zhijun ; Lu, Cheng ; He, Xiaojuan ; Au, D. W T ; Pan, Xiaohua ; Zhang, Bao-Ting ; Lu, Changwei ; Zhang, Hongqi ; Yue, Kinman ; Qian, Airong ; Shang, Peng ; Xu, Jiake ; Xiao, Lianbo ; Bian, Zhaoxiang ; Tan, Weihong ; Liang, Zicai ; He, Fuchu ; Zhang, Lingqiang ; Lu, Aiping ; Zhang, Ge. / Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. In: Nature Medicine. 2015 ; Vol. 21, No. 3. pp. 288-294.