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

Journal of Nanobiotechnology

Research

Smita Kulkarni¹  Leila Fotooh Abadi¹  Virendra Gajbhiye²  Pramod Kumar²  Kishore Paknikar³ 

[1] Division of Virology, Indian Council of Medical Research-National AIDS Research Institute, 411 026, Pune, India;Nanobioscience Group, Agharkar Research Institute, 411 004, Pune, India;Nanobioscience Group, Agharkar Research Institute, 411 004, Pune, India;Department of Chemistry, Indian Institute of Technology, 400 076, Mumbai, India;

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

DOI  :  10.1186/s12951-022-01750-w

 received in 2022-03-23, accepted in 2022-12-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsTNF-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.ConclusionsWe 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.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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