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Delivery of Small Genetic Molecules through Hollow Porous Nanoparticles Silences Target Gene and in Turn Stimulates Osteoblastic Differentiation
Author(s) -
Kim JungJu,
Singh Rajendra K.,
Patel Kapil D.,
Kim HaeWon
Publication year - 2016
Publication title -
particle and particle systems characterization
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.877
H-Index - 56
eISSN - 1521-4117
pISSN - 0934-0866
DOI - 10.1002/ppsc.201600098
Subject(s) - nanocarriers , runx2 , microbiology and biotechnology , small interfering rna , gene silencing , nanoshell , intracellular , chemistry , biophysics , rna interference , gene expression , nanotechnology , materials science , nanoparticle , gene , transfection , biology , rna , biochemistry
Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho‐1 gene. In particular, a pressure‐induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained ≈30% is almost three times higher than that of a non‐hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion‐controlled manner, in striking contrast to the rapid release (3 d) from a non‐hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA‐nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho‐1 expression down to 20%, which in turn up‐regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair.