Indexed by:期刊论文

Date of Publication:2018-10-01

Journal:NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE

Included Journals:PubMed、SCIE

Volume:14

Issue:7

Page Number:2143-2153

ISSN No.:1549-9634

Key Words:Targeted drug delivery; Lipid-polymer hybrid nanoparticles; alpha 4 beta 7 Monoclonal antibody; GALT; Gut-homing T cell; HIV-1

Abstract:A major sanctuary site for HIV infection is the gut-associated lymphoid tissue (GALT). The alpha 4 beta 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 alpha 4 beta 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 alpha 4 beta 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 alpha 4 beta 7+ cells. Our LCNP shows the potential to co-deliver ARVs and mAbs for eradicating HIV reservoirs. (c) 2018 Elsevier Inc. All rights reserved.