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NEUROSCIENCE
Organically modified silica nanoparticles: A nonviral vector for in vivo gene delivery and expression in the brain
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*Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York, Buffalo, NY 14260; Molecular and Structural Neurobiology and Gene Therapy Program, Department of Pathology and Anatomical Sciences, State University of New York, Buffalo, NY 14214; and Department of Anatomy and Neurobiology, Medical University of Gdansk, 80-210 Gdansk, Poland
Communicated by Tobin J. Marks, Northwestern University, Evanston, IL, June 13,2005 (received for review March 28, 2005)
This article reports on the application of organically modified silica (ORMOSIL) nanoparticles as a nonviral vector for efficient in vivo gene delivery. Highly monodispersed, stable aqueous suspension of nanoparticles, surface-functionalized with amino groups for binding of DNA, were prepared and characterized. Stereotaxic injections of nanoparticles, complexed with plasmid DNA encoding for EGFP, into the mouse ventral midbrain and into lateral ventricle, allowed us to fluorescently visualize the extensive transfection of neuronal-like cells in substantia nigra and areas surrounding the lateral ventricle. No ORMOSIL-based toxicity was observed 4 weeks after transfection. The efficiency of transfection equaled or exceeded that obtained in studies using a viral vector. An in vivo optical imaging technique (a fiber-based confocal fluorescent imaging system) provided an effective means to show the retention of viability of the transfected cells. The ORMOSIL-mediated transfections also were used to manipulate the biology of the neural stem/progenitor cells in vivo. Transfection of a plasmid expressing the nucleus-targeting fibroblast growth factor receptor type 1 resulted in significant inhibition of the in vivo incorporation of bromodeoxyuridine into the DNA of the cells in the subventricular zone and the adjacent rostral migratory stream. This in vivo approach shows that the nuclear receptor can control the proliferation of the stem/progenitor cells in this region of the brain. The results of this nanomedicine approach using ORMOSIL nanoparticles as a nonviral gene delivery platform have a promising future direction for effective therapeutic manipulation of the neural stem/progenitor cells as well as in vivo targeted brain therapy.
gene transfection | neurological | stem | progenitor cells
Abbreviations: ORMOSIL, organically modified silica; SVZ, subventricular zone; NSPC, neural stem/progenitor cell; FGFR1, FGF receptor type 1; NLS, nuclear localization signal; NGS, normal goat serum; SN, substantia nigra; SNc, SN par compacta; TH, tyrosine hydroxylase; LV, lateral ventricle; SP, signal peptide.
Freely available online through the PNAS open access option.
To whom correspondence may be addressed. E-mail: pnprasad{at}buffalo.edu or mks4{at}acsu.buffalo.edu.
© 2005 by The National Academy of Sciences of the USA
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