1. Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection
- Author
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Fulcher, Jennifer A, Tamshen, Kyle, Wollenberg, Alexander L, Kickhoefer, Valerie A, Mrazek, Jan, Elliott, Julie, Ibarrondo, F Javier, Anton, Peter A, Rome, Leonard H, Maynard, Heather D, Deming, Timothy, and Yang, Otto O
- Subjects
Biochemistry and Cell Biology ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Biological Sciences ,Infectious Diseases ,HIV/AIDS ,Biotechnology ,Bioengineering ,Nanotechnology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Anti-Retroviral Agents ,Cells ,Cultured ,Cytoplasm ,Drug Delivery Systems ,Drug Liberation ,HIV Infections ,HIV-1 ,Humans ,Leukocytes ,Mononuclear ,Nanoparticles ,Ribonucleoproteins ,Organic Chemistry ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1.
- Published
- 2019