학술논문
Nanomedicine platform for targeting activated neutrophils and neutrophil–platelet complexes using an α1-antitrypsin-derived peptide motif
Document Type
article
Author
Cruz, Michelle A; Bohinc, Dillon; Andraska, Elizabeth A; Alvikas, Jurgis; Raghunathan, Shruti; Masters, Nicole A; van Kleef, Nadine D; Bane, Kara L; Hart, Kathryn; Medrow, Kathryn; Sun, Michael; Liu, Haitao; Haldeman, Shannon; Banerjee, Ankush; Lessieur, Emma M; Hageman, Kara; Gandhi, Agharnan; de la Fuente, Maria; Nieman, Marvin T; Kern, Timothy S; Maas, Coen; de Maat, Steven; Neeves, Keith B; Neal, Matthew D; Sen Gupta, Anirban; Stavrou, Evi X
Source
Nature Nanotechnology. 17(9)
Subject
Language
Abstract
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.