Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept
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/A...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01750-w |
| _version_ | 1828056710872301568 |
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| author | Leila Fotooh Abadi Pramod Kumar Kishore Paknikar Virendra Gajbhiye Smita Kulkarni |
| author_facet | Leila Fotooh Abadi Pramod Kumar Kishore Paknikar Virendra Gajbhiye Smita Kulkarni |
| author_sort | Leila Fotooh Abadi |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| first_indexed | 2024-04-10T20:59:51Z |
| format | Article |
| id | doaj.art-5b8ec1f8c57848309cc06b70ab07004a |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-10T20:59:51Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5b8ec1f8c57848309cc06b70ab07004a2023-01-22T12:24:01ZengBMCJournal of Nanobiotechnology1477-31552023-01-0121112410.1186/s12951-022-01750-wTenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of conceptLeila Fotooh Abadi0Pramod Kumar1Kishore Paknikar2Virendra Gajbhiye3Smita Kulkarni4Division of Virology, Indian Council of Medical Research-National AIDS Research InstituteNanobioscience Group, Agharkar Research InstituteNanobioscience Group, Agharkar Research InstituteNanobioscience Group, Agharkar Research InstituteDivision of Virology, Indian Council of Medical Research-National AIDS Research InstituteAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01750-wNanoARTLong-acting antiretroviralGenotoxicologyHIV reservoirsPreclinicalBiodistribution |
| spellingShingle | Leila Fotooh Abadi Pramod Kumar Kishore Paknikar Virendra Gajbhiye Smita Kulkarni 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 NanoART Long-acting antiretroviral Genotoxicology HIV reservoirs Preclinical Biodistribution |
| title | Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept |
| title_full | Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept |
| title_fullStr | Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept |
| title_full_unstemmed | Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept |
| title_short | Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept |
| title_sort | tenofovir tethered gold nanoparticles as a novel multifunctional long acting anti hiv therapy to overcome deficient drug delivery an in vivo proof of concept |
| topic | NanoART Long-acting antiretroviral Genotoxicology HIV reservoirs Preclinical Biodistribution |
| url | https://doi.org/10.1186/s12951-022-01750-w |
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