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Nanomedicine. 2018 Oct;14(7):2143-2153. doi: 10.1016/j.nano.2018.06.005. Epub 2018 Jun 28.

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

Author information

1
Department of Bioengineering, University of Washington, Seattle, USA.
2
Department of Bioengineering, University of Washington, Seattle, USA; Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology 116023, Dalian, China; Research Center for the Control Engineering of Translational Precision Medicine, Dalian University of Technology 116023, Dalian, China.
3
Department of Bioengineering, University of Washington, Seattle, USA. Electronic address: woodrow@uw.edu.

Abstract

A major sanctuary site for HIV infection is the gut-associated lymphoid tissue (GALT). The α4β7 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 α4β7 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 α4β7 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 α4β7+ cells. Our LCNP shows the potential to co-deliver ARVs and mAbs for eradicating HIV reservoirs.

KEYWORDS:

GALT; Gut-homing T cell; HIV-1; Lipid-polymer hybrid nanoparticles; Targeted drug delivery; α4β7 Monoclonal antibody

PMID:
29964219
DOI:
10.1016/j.nano.2018.06.005
[Indexed for MEDLINE]

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