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

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 ZhangKinman Yue, Airong Qian, Peng Shang, Jiake Xu, Lianbo Xiao, Zhaoxiang Bian, Weihong Tan, Zicai Liang, Fuchu He, Lingqiang Zhang^*, Aiping Lu^*, Ge Zhang^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

331 Citations (Scopus)

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.

Original language	English
Pages (from-to)	288-294
Journal	Nature Medicine
Volume	21
Issue number	3
Online published	9 Feb 2015
DOIs	https://doi.org/10.1038/nm.3791
Publication status	Published - Mar 2015

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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

@article{935e40ace71d45efbdc6fcd6617dc4fe,

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

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.",

author = "Chao Liang and Baosheng Guo and Heng Wu and Ningsheng Shao and Defang Li and Jin Liu and Lei Dang and Cheng Wang and Hui Li and Shaohua Li and Lau, {Wing Ki} and Yu Cao and Zhijun Yang and Cheng Lu and Xiaojuan He and Au, {D. W T} and Xiaohua Pan and Bao-Ting Zhang and Changwei Lu and Hongqi Zhang and Kinman Yue and Airong Qian and Peng Shang and Jiake Xu and Lianbo Xiao and Zhaoxiang Bian and Weihong Tan and Zicai Liang and Fuchu He and Lingqiang Zhang and Aiping Lu and Ge Zhang",

year = "2015",

month = mar,

doi = "10.1038/nm.3791",

language = "English",

volume = "21",

pages = "288--294",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "3",

}

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

TY - JOUR

T1 - Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy

AU - Liang, Chao

AU - Guo, Baosheng

AU - Wu, Heng

AU - Shao, Ningsheng

AU - Li, Defang

AU - Liu, Jin

AU - Dang, Lei

AU - Wang, Cheng

AU - Li, Hui

AU - Li, Shaohua

AU - Lau, Wing Ki

AU - Cao, Yu

AU - Yang, Zhijun

AU - Lu, Cheng

AU - He, Xiaojuan

AU - Au, D. W T

AU - Pan, Xiaohua

AU - Zhang, Bao-Ting

AU - Lu, Changwei

AU - Zhang, Hongqi

AU - Yue, Kinman

AU - Qian, Airong

AU - Shang, Peng

AU - Xu, Jiake

AU - Xiao, Lianbo

AU - Bian, Zhaoxiang

AU - Tan, Weihong

AU - Liang, Zicai

AU - He, Fuchu

AU - Zhang, Lingqiang

AU - Lu, Aiping

AU - Zhang, Ge

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-84925516251&origin=recordpage

U2 - 10.1038/nm.3791

DO - 10.1038/nm.3791

M3 - RGC 21 - Publication in refereed journal

C2 - 25665179

SN - 1078-8956

VL - 21

SP - 288

EP - 294

JO - Nature Medicine

JF - Nature Medicine

IS - 3

ER -

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

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