Core-shell nanoparticles for targeted and combination antiretroviral activity in gut-homing T cells.
Nanomedicine
; 14(7): 2143-2153, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29964219
ABSTRACT
A major sanctuary site for HIV infection is the gut-associated lymphoid tissue (GALT). The α4ß7 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 α4ß7 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 α4ß7 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 α4ß7+ cells. Our LCNP shows the potential to co-deliver ARVs and mAbs for eradicating HIV reservoirs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Linfócitos T
/
Integrinas
/
Fármacos Anti-HIV
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Nanopartículas
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Intestino Delgado
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Anticorpos Monoclonais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos