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

46 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.

LanguageEnglish
Pages6884-6893
Number of pages10
JournalACS Nano
Volume7
Issue number8
Early online date26 Jul 2013
DOIs
Publication statusPublished - 27 Aug 2013
Externally publishedYes

Fingerprint

influenza
Porous silicon
Influenza A virus
viruses
infectious diseases
Silicon
Virus Diseases
porous silicon
Viruses
Nanoparticles
nanoparticles
Antiviral Agents
Solubility
Vacuolar Proton-Translocating ATPases
Madin Darby Canine Kidney Cells
Retinal Pigment Epithelium
Endosomes
Pandemics
drugs
In Vitro Techniques

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

Cite this

Bimbo, L. M., Denisova, O. V., Mäkilä, E., Kaasalainen, M., De Brabander, J. K., Hirvonen, J., ... Santos, H. A. (2013). Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles. ACS Nano, 7(8), 6884-6893. https://doi.org/10.1021/nn402062f
Bimbo, Luis M. ; Denisova, Oxana V. ; Mäkilä, Ermei ; Kaasalainen, Martti ; De Brabander, Jef K. ; Hirvonen, Jouni ; Salonen, Jarno ; Kakkola, Laura ; Kainov, Denis ; Santos, Hélder A. / Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles. In: ACS Nano. 2013 ; Vol. 7, No. 8. pp. 6884-6893.
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Bimbo, LM, Denisova, OV, Mäkilä, E, Kaasalainen, M, De Brabander, JK, Hirvonen, J, Salonen, J, Kakkola, L, Kainov, D & Santos, HA 2013, 'Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles' ACS Nano, vol. 7, no. 8, pp. 6884-6893. https://doi.org/10.1021/nn402062f

Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles. / Bimbo, Luis M.; Denisova, Oxana V.; Mäkilä, Ermei; Kaasalainen, Martti; De Brabander, Jef K.; Hirvonen, Jouni; Salonen, Jarno; Kakkola, Laura; Kainov, Denis; Santos, Hélder A.

In: ACS Nano, Vol. 7, No. 8, 27.08.2013, p. 6884-6893.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles

AU - Bimbo, Luis M.

AU - Denisova, Oxana V.

AU - Mäkilä, Ermei

AU - Kaasalainen, Martti

AU - De Brabander, Jef K.

AU - Hirvonen, Jouni

AU - Salonen, Jarno

AU - Kakkola, Laura

AU - Kainov, Denis

AU - Santos, Hélder A.

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Y1 - 2013/8/27

N2 - 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.

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KW - drug delivery systems

KW - animals

KW - silicon

KW - drug carriers

KW - storage

KW - humans

KW - Influenza A virus

KW - Madin-Darby canine kidney cells

KW - microscopy

KW - chemical models

KW - nanoparticles

KW - nanotechnology

KW - particle size

KW - salicylates

KW - solvents

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Bimbo LM, Denisova OV, Mäkilä E, Kaasalainen M, De Brabander JK, Hirvonen J et al. Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles. ACS Nano. 2013 Aug 27;7(8):6884-6893. https://doi.org/10.1021/nn402062f