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.
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China. [4] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [5] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [7] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [8] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Chao
authors: C
authors: Liang
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [4] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [7] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Baosheng
authors: B
authors: Guo
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China.
authors: Heng
authors: H
authors: Wu
authors: Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Science, Beijing, China.
authors: Ningsheng
authors: N
authors: Shao
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [6] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Defang
authors: D
authors: Li
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [6] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Jin
authors: J
authors: Liu
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [6] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Lei
authors: L
authors: Dang
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an, China.
authors: Cheng
authors: C
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Science, Beijing, China.
authors: Hui
authors: H
authors: Li
authors: Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Science, Beijing, China.
authors: Shaohua
authors: S
authors: Li
authors: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors: Wing Ki
authors: WK
authors: Lau
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Yu
authors: Y
authors: Cao
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China.
authors: Zhijun
authors: Z
authors: Yang
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [4] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [7] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.
authors: Cheng
authors: C
authors: Lu
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [4] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China.
authors: Xiaojuan
authors: X
authors: He
authors: Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China.
authors: D W T
authors: DW
authors: Au
authors: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors: Xiaohua
authors: X
authors: Pan
authors: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors: Bao-Ting
authors: BT
authors: Zhang
authors: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors: Changwei
authors: C
authors: Lu
authors: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors: Hongqi
authors: H
authors: Zhang
authors: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors: Kinman
authors: K
authors: Yue
authors: 1] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China. [2] Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an, China.
authors: Airong
authors: A
authors: Qian
authors: 1] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China. [2] Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an, China.
authors: Peng
authors: P
authors: Shang
authors: Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia.
authors: Jiake
authors: J
authors: Xu
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China.
authors: Lianbo
authors: L
authors: Xiao
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [3] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [4] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China.
authors: Zhaoxiang
authors: Z
authors: Bian
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [3] Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China. [4] College of Biology, Hunan University, Changsha, China. [5] Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha, China. [6] Department of Chemistry, University of Florida, Gainesville, Florida, USA. [7] Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA. [8] Center for Research at Bio/Nano Interface, Shands Cancer Center, University of Florida, Gainesville, Florida, USA.
authors: Weihong
authors: W
authors: Tan
authors: Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China.
authors: Zicai
authors: Z
authors: Liang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Fuchu
authors: F
authors: He
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Lingqiang
authors: L
authors: Zhang
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [4] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [7] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China. [8] Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China.
authors: Aiping
authors: A
authors: Lu
authors: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. [2] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. [3] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China. [4] Institute of Integrated Bioinfomedicine &Translational Science, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [5] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, Shenzhen, China. [6] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong, China. [7] Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China. [8] Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an, China. [9] Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China.
authors: Ge
authors: G
authors: Zhang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000235:genetics; D008055:Lipids; D053758:Nanoparticles; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats
chemical_list: D052157:Aptamers, Nucleotide; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; C408877:PLEKHO1 protein, human; D034741:RNA, Small Interfering