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Nat Nanotechnol ; 17(9): 1004-1014, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35851383

RESUMEN

Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α1-antitrypsin-derived peptide to confer binding specificity to neutrophil elastase on activated neutrophils. Surface decoration with this peptide enabled specific anchorage of nanoparticles to activated neutrophils and platelet-neutrophil aggregates, in vitro and in vivo. Nanoparticle delivery of a model drug, hydroxychloroquine, demonstrated significant reduction of neutrophil activities in vitro and a therapeutic effect on murine venous thrombosis in vivo. This innovative approach of cell-specific and activation-state-specific targeting can be applied to several neutrophil-driven pathologies.


Asunto(s)
Elastasa de Leucocito , Deficiencia de alfa 1-Antitripsina , Animales , Humanos , Hidroxicloroquina/farmacología , Elastasa de Leucocito/metabolismo , Ratones , Nanomedicina , Neutrófilos
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