@article{e2f9b34701b44a9aa38b978277fd5c1f,
title = "Nanomedicine platform for targeting activated neutrophils and neutrophil-platelet complexes using an α1-antitrypsin-derived peptide motif",
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",
author = "Cruz, \{Michelle A\} and Dillon Bohinc and Andraska, \{Elizabeth A\} and Jurgis Alvikas and Shruti Raghunathan and Masters, \{Nicole A\} and \{van Kleef\}, \{Nadine D\} and Bane, \{Kara L\} and Kathryn Hart and Kathryn Medrow and Michael Sun and Haitao Liu and Shannon Haldeman and Ankush Banerjee and Lessieur, \{Emma M\} and Kara Hageman and Agharnan Gandhi and \{de la Fuente\}, Maria and Nieman, \{Marvin T\} and Kern, \{Timothy S\} and Coen Maas and \{de Maat\}, Steven and Neeves, \{Keith B\} and Neal, \{Matthew D\} and \{Sen Gupta\}, Anirban and Stavrou, \{Evi X\}",
note = "Funding Information: We thank the Hematopoietic Biorepository Core of Case Western Reserve University for human blood sample provision; M. Sramkoski at the Case Western Reserve University Cancer Center Flow Cytometry core facility; S. Bandyopadhyay at the Cleveland Clinic for assistance with BiaCore studies; and G. Deshpande and the Cleveland Clinic Lerner Research Institute Imaging Core for expert histologic analysis. This work was supported by the National Institutes of Health R01 HL137695 (E.X.S.); R01 HL129179, R01 HL137695, R01 HL141080, R01 HL121212 (A.S.G.); R33HL141794, R01HL120728, R01HL151984 (K.B.N.); R35 GM119526, R01 HL141080 (M.D.N.); R01 HL098217 (M.T.N.); EY022938, R24 EY024864 (T.S.K.); F32 HL149207 (J.A.); the Clinical and Translational Science Collaborative of Cleveland [UL1TR002548 from the National Center for Advancing Translational Sciences component of the National Institutes of Health and National Institutes of Health roadmap for Medical Research (E.X.S., A.S.G.)]; Merit Review Awards (BX003851 (E.X.S.) and BX003604 (T.S.K.) from the Department of Veterans Affairs); a Case Coulter Translational Research Partnership Award (RES514649 (E.X.S., A.S.G.)); a University of Pittsburgh Physician-Scientist Award from the Burroughs Wellcome Fund (E.A.A., J.A.); a T-32 PostDoctoral Training award [NIH T32HL098036 (E.A.A.)]; an American Heart Association Scientist Development Award (E.X.S.); and the Oscar D. Ratnoff Endowed Professorship (E.X.S.). We acknowledge an unrestricted grant to the Department of Ophthalmology from Research to Prevent Blindness (New York, NY; T.S.K.). S.d.M. gratefully acknowledges the Toegepaste en Technische Wetenschappen (TTW) section of the Netherlands Organization for Scientific Research (NWO, 2019/TTW/00704802). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs or the United States Government. Funding Information: We thank the Hematopoietic Biorepository Core of Case Western Reserve University for human blood sample provision; M. Sramkoski at the Case Western Reserve University Cancer Center Flow Cytometry core facility; S. Bandyopadhyay at the Cleveland Clinic for assistance with BiaCore studies; and G. Deshpande and the Cleveland Clinic Lerner Research Institute Imaging Core for expert histologic analysis. This work was supported by the National Institutes of Health R01 HL137695 (E.X.S.); R01 HL129179, R01 HL137695, R01 HL141080, R01 HL121212 (A.S.G.); R33HL141794, R01HL120728, R01HL151984 (K.B.N.); R35 GM119526, R01 HL141080 (M.D.N.); R01 HL098217 (M.T.N.); EY022938, R24 EY024864 (T.S.K.); F32 HL149207 (J.A.); the Clinical and Translational Science Collaborative of Cleveland [UL1TR002548 from the National Center for Advancing Translational Sciences component of the National Institutes of Health and National Institutes of Health roadmap for Medical Research (E.X.S., A.S.G.)]; Merit Review Awards (BX003851 (E.X.S.) and BX003604 (T.S.K.) from the Department of Veterans Affairs); a Case Coulter Translational Research Partnership Award (RES514649 (E.X.S., A.S.G.)); a University of Pittsburgh Physician-Scientist Award from the Burroughs Wellcome Fund (E.A.A., J.A.); a T-32 PostDoctoral Training award [NIH T32HL098036 (E.A.A.)]; an American Heart Association Scientist Development Award (E.X.S.); and the Oscar D. Ratnoff Endowed Professorship (E.X.S.). We acknowledge an unrestricted grant to the Department of Ophthalmology from Research to Prevent Blindness (New York, NY; T.S.K.). S.d.M. gratefully acknowledges the Toegepaste en Technische Wetenschappen (TTW) section of the Netherlands Organization for Scientific Research (NWO, 2019/TTW/00704802). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs or the United States Government. Publisher Copyright: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2022",
month = sep,
doi = "10.1038/s41565-022-01161-w",
language = "English",
volume = "17",
pages = "1004--1014",
journal = "Nature nanotechnology",
issn = "1748-3387",
publisher = "Nature Research",
number = "9",
}