Phenylboronic-acid-modified nanoparticles: potential antiviral therapeutics

ACS Appl Mater Interfaces. 2013 Dec 11;5(23):12488-98. doi: 10.1021/am403770q. Epub 2013 Nov 19.

Abstract

Phenylboronic-acid-modified nanoparticles (NPs) are attracting considerable attention for biological and biomedical applications. We describe here a convenient and general protocol for attaching multiple copies of para-substituted phenylboronic acid moieties onto either iron-oxide-, silica- or diamond-derived NPs. The boronic acid functionalized NPs are all fabricated by first modifying the surface of each particle type with 4-azidobenzoic ester functions. These azide-terminated nanostructures were then reacted with 4-[1-oxo-4-pentyn-1-yl) amino]phenylboronic acid units via a Cu(I) catalyzed Huisgen cycloaddition to furnish, conveniently, the corresponding boronic-acid modified NPs (or "borono-lectins") targeted in this work. The potential of these novel "borono-lectins" as antiviral inhibitors was investigated against the Hepatitis C virus (HCV) exploiting a bioassay that measures the potential of drugs to interfere with the ability of cell-culture-derived JFH1 virus particles to infect healthy hepatocytes. As far as we are aware, this is the first report that describes NP-derived viral entry inhibitors and thus serves as a "proof-of-concept" study. The novel viral entry activity demonstrated, and the fact that the described boronic-acid-functionalized NPs all display much reduced cellular toxicities compared with alternate NPs, sets the stage for their further investigation. The data supports that NP-derived borono-lectins should be pursued as a potential therapeutic strategy for blocking viral entry of HCV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Boronic Acids / chemistry*
  • Magnetic Resonance Spectroscopy
  • Nanoparticles*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Antiviral Agents
  • Boronic Acids
  • benzeneboronic acid