Boronic acid-modified lipid nanocapsules: A novel platform for the highly efficient inhibition of hepatitis C viral entry

Manakamana Khanal, Alexandre Barras, Thibaut Vausselin, Lucie Fénéant, Rabah Boukherroub, Aloysius Siriwardena, Jean Dubuisson, Sabine Szunerits

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The search for viral entry inhibitors that selectively target viral envelope glycoproteins has attracted increasing interest in recent years. Amongst the handful of molecules reported to show activity as hepatitis C virus (HCV) entry inhibitors are a variety of glycan-binding proteins including the lectins, cyanovirin-N (CV-N) and griffithsin. We recently demonstrated that boronic acid-modified nanoparticles are able to reduce HCV entry through a similar mechanism to that of lectins. A major obstacle to any further development of these nanostructures as viral entry inhibitors is their only moderate maximal inhibition potential. In the present study, we report that lipid nanocapsules (LNCs), surface-functionalized with amphiphilic boronic acid (BA) through their post-insertion into the semi-rigid shell of the LNCs, are indeed far superior as HCV entry inhibitors when compared with previously reported nanostructures. These 2nd generation particles (BA-LNCs) are shown to prevent HCV infection in the micromolar range (IC50 = 5.4 μM of BA moieties), whereas the corresponding BA monomers show no significant effects even at the highest analyzed concentration (20 μM). The new BA-LNCs are the most promising boronolectin-based HCV entry inhibitors reported to date and are thus observed to show great promise in the development of a pseudolectin-based therapeutic agent.

Original languageEnglish
Pages (from-to)1392-1402
Number of pages11
JournalNanoscale
Volume7
Issue number4
DOIs
StatePublished - 28 Jan 2015
Externally publishedYes

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