Journal
NANOSCALE RESEARCH LETTERS
Volume 10, Issue -, Pages -Publisher
SPRINGEROPEN
DOI: 10.1186/s11671-015-1112-z
Keywords
HIV-1; CD45RO; Memory T cells; Nanoparticles
Funding
- Open Research Fund Program of the State Key Laboratory of Virology of the People's Republic of China [2014KF004]
- National Natural Science Fund [81572431]
- the Anhui College Students' Innovation and Entrepreneurship Training Plan [20151036317, AH201410361087, AH201410361263, AH201410361264, AH201410361266, AH201410361269]
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Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA-and SAHA + Nel-loaded nanoparticles can target latently infected CD4(+) T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.
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