Nanomedicine platform for targeting activated neutrophils and neutrophil-platelet complexes using an α1-antitrypsin-derived peptide motif
Publication date
2022-09
Authors
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
Editors
Advisors
Supervisors
Document Type
Article
Metadata
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License
taverne
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 α 1-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.
Keywords
Animals, Humans, Hydroxychloroquine/pharmacology, Leukocyte Elastase/metabolism, Mice, Nanomedicine, Neutrophils, alpha 1-Antitrypsin Deficiency, Taverne, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Citation
Cruz, M A, Bohinc, D, Andraska, E A, Alvikas, J, Raghunathan, S, Masters, N A, van Kleef, N D, Bane, K L, Hart, K, Medrow, K, Sun, M, Liu, H, Haldeman, S, Banerjee, A, Lessieur, E M, Hageman, K, Gandhi, A, de la Fuente, M, Nieman, M T, Kern, T S, Maas, C, de Maat, S, Neeves, K B, Neal, M D, Sen Gupta, A & Stavrou, E X 2022, 'Nanomedicine platform for targeting activated neutrophils and neutrophil-platelet complexes using an α1-antitrypsin-derived peptide motif', Nature nanotechnology, vol. 17, no. 9, pp. 1004-1014. https://doi.org/10.1038/s41565-022-01161-w