Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles
nanoparticles, porous silicon, chitosan, gene delivery
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.
Tsinghua University Press
Morteza Hasanzadeh Kafshgari,Bahman Delalat,Wing Yin Tong,Frances J. Harding,Martti Kaasalainen,Jarno Salonen,Nicolas H. Voelcker, Oligonucleotide delivery by chitosan-functionalized porous silicon nanoparticles. NanoRes.2015, 8(6): 2033–2046