Core-shell nanoparticles for targeted and combination antiretroviral activity in gut-homing T cells.

ABSTRACT: A major sanctuary site for HIV infection is the gut-associated lymphoid tissue (GALT). The ?4?7 integrin gut homing receptor is a promising therapeutic target for the virus reservoir because it leads to migration of infected cells to the GALT and facilitates HIV infection. Here, we developed a core-shell nanoparticle incorporating the ?4?7 monoclonal antibody (mAb) as a dual-functional ligand for selectively targeting a protease inhibitor (PI) to gut-homing T cells in the GALT while simultaneously blocking HIV infection. Our nanoparticles significantly reduced cytotoxicity of the PI and enhanced its in vitro antiviral activity in combination with ?4?7 mAb. We demonstrate targeting function of our nanocarriers in a human T cell line and primary cells isolated from macaque ileum, and observed higher in vivo biodistribution to the murine small intestines where they accumulate in ?4?7+ cells. Our LCNP shows the potential to co-deliver ARVs and mAbs for eradicating HIV reservoirs.

SUBMITTER: Cao S 

PROVIDER: S-EPMC6545289 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature