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Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles

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Abstract

Porous silicon nanoparticles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and characterization of thermally hydrocarbonized pSiNPs (THCpSiNPs) and chitosan-coated THCpSiNPs for therapeutic oligonucleotide delivery. Chitosan coating after oligonucleotide loading significantly improves sustained oligonucleotide release and suppresses burst release effects. Moreover, cellular uptake, endocytosis, and cytotoxicity of oligonucleotide-loaded THCpSiNPs have been evaluated in vitro. Standard cell viability assays demonstrate that cells incubated with the NPs at a concentration of 0.1 mg/mL are 95% viable. In addition, chitosan coating significantly enhances the uptake of oligonucleotide-loaded THCpSiNPs across the cell membrane. Moreover, histopathological analysis of liver, kidney, spleen, and skin tissue collected from mice receiving NPs further demonstrates the biocompatible and non-inflammatory properties of the NPs as a gene delivery vehicle for intravenous and subcutaneous administration in vivo. Taken together, these results suggest that THCpSiNPs provide a versatile platform that could be used as efficient vehicles for the intracellular delivery of oligonucleotides for gene therapy.

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Authors and Affiliations

  1. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Mawson Institute, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia

    Morteza Hasanzadeh Kafshgari, Bahman Delalat, Wing Yin Tong, Frances J. Harding & Nicolas H. Voelcker

  2. Department of Physics and Astronomy, University of Turku, FI-20014, Turku, Finland

    Martti Kaasalainen & Jarno Salonen

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  1. Morteza Hasanzadeh Kafshgari
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  2. Bahman Delalat
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  3. Wing Yin Tong
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  4. Frances J. Harding
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  5. Martti Kaasalainen
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  6. Jarno Salonen
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  7. Nicolas H. Voelcker
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Correspondence to Nicolas H. Voelcker.

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Kafshgari, M.H., Delalat, B., Tong, W.Y. et al. Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles. Nano Res. 8, 2033–2046 (2015). https://doi.org/10.1007/s12274-015-0715-0

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