1. Nanomedicine platform for targeting activated neutrophils and neutrophil–platelet complexes using an α1-antitrypsin-derived peptide motif
- Author
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Michelle A. Cruz, Dillon Bohinc, Elizabeth A. Andraska, Jurgis Alvikas, Shruti Raghunathan, Nicole A. Masters, Nadine D. van Kleef, Kara L. Bane, Kathryn Hart, Kathryn Medrow, Michael Sun, Haitao Liu, Shannon Haldeman, Ankush Banerjee, Emma M. Lessieur, Kara Hageman, Agharnan Gandhi, Maria de la Fuente, Marvin T. Nieman, Timothy S. Kern, Coen Maas, Steven de Maat, Keith B. Neeves, Matthew D. Neal, Anirban Sen Gupta, and Evi X. Stavrou
- Subjects
Neutrophils ,Biomedical Engineering ,Bioengineering ,Hematology ,Condensed Matter Physics ,Article ,Atomic and Molecular Physics, and Optics ,Mice ,Nanomedicine ,Clinical Research ,5.1 Pharmaceuticals ,alpha 1-Antitrypsin Deficiency ,Nanoparticles ,Animals ,Humans ,Nanotechnology ,General Materials Science ,Development of treatments and therapeutic interventions ,Nanoscience & Nanotechnology ,Electrical and Electronic Engineering ,Leukocyte Elastase ,Hydroxychloroquine - 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.
- Published
- 2022