Integrin-supported fast rate intracellular delivery of plasmid DNA by extracellular matrix protein embedded calcium phosphate complexes.
Extracellular matrix (ECM) proteins, such as collagen and fibronectin, play vital roles in development and maintenance of hard tissue (bone or tooth) and are, consequently, thoroughly investigated for construction of biomimetic scaffolds in combination with calcium phosphate (CaP) material (the major component of hard tissue) for bone or dental tissue engineering. Realizing the natural affinity of ECM components toward inorganic constituents of hard tissue, we successfully constructed the nanohybrids of DNA/CaP particles with either collagen 1 or fibronectin, which finally possessed the capability of specific recognition of integrin receptor for being swiftly internalized across the plasma membrane, leading to remarkably high transgene expression in mammalian cells. This new approach with precise receptor-specific delivery as well as 10- to 50-fold enhanced efficiency level compared to the classical one, has immediate applications for basic research and large scale production of recombinant therapeutic proteins and looks promising for gene therapy.
Chowdhury
E H
EH
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Nagaoka
M
M
Ogiwara
K
K
Zohra
F T
FT
Kutsuzawa
K
K
Tada
S
S
Kitamura
C
C
Akaike
T
T
D016475:3T3 Cells; D000818:Animals; D002130:Calcium Phosphates / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D010957:Plasmids / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D002130:Calcium Phosphates; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D003094:Collagen