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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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Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles

Show Author's information Morteza Hasanzadeh Kafshgari1,§Bahman Delalat1,§Wing Yin Tong1Frances J. Harding1Martti Kaasalainen2Jarno Salonen2Nicolas H. Voelcker1( )
ARC Centre of Excellence in Convergent Bio-Nano Science and TechnologyMawson InstituteUniversity of South AustraliaGPO Box 2471AdelaideSA5001Australia
Department of Physics and AstronomyUniversity of TurkuFI-20014Turku, Finland

§These authors contributed equally to this work.

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.

Keywords: nanoparticles, chitosan, gene delivery, porous silicon

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Publication history
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Acknowledgements

Publication history

Received: 03 August 2014
Revised: 07 January 2015
Accepted: 07 January 2015
Published: 22 April 2015
Issue date: June 2015

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2015

Acknowledgements

Acknowledgements

This research was conducted and funded by the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (No. CE140100036). M. H. K. thanks the Australian Nanotechnology Network and the Finnish Centre for International Mobility (CIMO Fellowship Programme) for awarding him an Overseas Travel Fellowships.

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