Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

J Nanobiotechnology. 2023 Jan 19;21(1):19. doi: 10.1186/s12951-022-01750-w.

Abstract

Background: The adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART.

Results: TNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs.

Conclusions: We show that the combination of TNF and AuNPs exhibits multifunctional activity, viz. anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS.

Keywords: Biodistribution; Genotoxicology; HIV reservoirs; In vivo imaging; Long-acting antiretroviral; NanoART; Nanomedicine; Preclinical.

MeSH terms

  • Acquired Immunodeficiency Syndrome* / drug therapy
  • Anti-HIV Agents* / pharmacology
  • Gold / therapeutic use
  • HIV Infections* / drug therapy
  • Humans
  • Metal Nanoparticles*
  • Peptide Hydrolases / therapeutic use
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use
  • Tissue Distribution

Substances

  • Tenofovir
  • Gold
  • Anti-HIV Agents
  • Peptide Hydrolases