Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles

Morteza Hasanzadeh Kafshgari, Bahman Delalat, Wing Yin Tong, Frances J. Harding, Martti Kaasalainen, Jarno Salonen, Nicolas H. Voelcker

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2033-2046
Number of pages14
JournalNano Research
Volume8
Issue number6
DOIs
Publication statusPublished - 22 Apr 2015
Externally publishedYes

Keywords

  • chitosan
  • gene delivery
  • nanoparticles
  • porous silicon

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