Format

Send to

Choose Destination
Nat Med. 2015 Mar;21(3):288-94. doi: 10.1038/nm.3791. Epub 2015 Feb 9.

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

Author information

1
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.
2
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.
3
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.
4
Department of Biochemistry and Molecular Biology, Beijing Institute of Basic Medical Science, Beijing, China.
5
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.
6
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.
7
Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
8
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
9
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.
10
Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China.
11
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
12
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.
13
Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia.
14
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.
15
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.
16
Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China.
17
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.
18
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.

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.

PMID:
25665179
PMCID:
PMC5508976
DOI:
10.1038/nm.3791
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center