Development and Evaluation of Peptide-Functionalized Gold Nanoparticles for HIV Integrase Inhibition

Abstract

The HIV integrase enzyme represents an important target for HIV inhibition because it is essential for viral replication and there is no cellular counterpart. Blocking HIV replication at this early stage of the viral life cycle can also prevent the establishment of viral reservoirs in the form of latently infected cells. Complications such as drug resistance and other adverse side effects associated with HIV treatment necessitate novel approaches for HIV inhibition. Nanoparticle-based systems are fast revolutionizing the biomedical field with applications in infectious disease diagnosis and treatment, and are important tools to investigate for HIV targeting. This study explores the development of gold nanoparticles functionalized with a hexapeptide, previously demonstrated to inhibit integrase at low micromolar concentrations. We also sought to investigate the effect of Tat peptide incorporation to facilitate both cellular and nuclear entry, so that both cytoplasmic and nuclear events mediated by integrase, could be targeted. Therefore, the aim of this study is to synthesize, characterize and evaluate the antiviral activity of nanoparticle-peptide complexes. Our results showed no obvious HIV inhibitory activity, but did provide original and fundamental in vitro data for this potent hexapeptide when challenged with HIV infection. Further insight into the optimization of gold nanoparticle functionalization with peptides is also provided.