Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles

Luis M. Bimbo, Oxana V. Denisova, Ermei Mäkilä, Martti Kaasalainen, Jef K. De Brabander, Jouni Hirvonen, Jarno Salonen, Laura Kakkola, Denis Kainov, Hélder A. Santos

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.

Original languageEnglish
Pages (from-to)6884-6893
Number of pages10
JournalACS Nano
Volume7
Issue number8
Early online date26 Jul 2013
DOIs
Publication statusPublished - 27 Aug 2013
Externally publishedYes

Keywords

  • drug delivery systems
  • animals
  • silicon
  • drug carriers
  • storage
  • humans
  • Influenza A virus
  • Madin-Darby canine kidney cells
  • microscopy
  • chemical models
  • nanoparticles
  • nanotechnology
  • particle size
  • salicylates
  • solvents

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