Targeted nanoparticles modify neutrophil function in vivo

Sandra Völs, Naomi Kaisar-Iluz, Merav E. Shaul, Arik Ryvkin, Haim Ashkenazy, Avishag Yehuda, Ronza Atamneh, Adina Heinberg, Meital Ben-David-Naim, Menucha Nadav, Shira Hirsch, Vera Mitesser, Seth J. Salpeter, Ron Dzikowski, Zvi Hayouka, Jonathan M. Gershoni, Zvi G. Fridlender*, Zvi Granot*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Neutrophils play critical roles in a broad spectrum of clinical conditions. Accordingly, manipulation of neutrophil function may provide a powerful immunotherapeutic approach. However, due to neutrophils characteristic short half-life and their large population number, this possibility was considered impractical. Here we describe the identification of peptides which specifically bind either murine or human neutrophils. Although the murine and human neutrophil-specific peptides are not cross-reactive, we identified CD177 as the neutrophil-expressed binding partner in both species. Decorating nanoparticles with a neutrophil-specific peptide confers neutrophil specificity and these neutrophil-specific nanoparticles accumulate in sites of inflammation. Significantly, we demonstrate that encapsulating neutrophil modifying small molecules within these nanoparticles yields specific modulation of neutrophil function (ROS production, degranulation, polarization), intracellular signaling and longevity both in vitro and in vivo. Collectively, our findings demonstrate that neutrophil specific targeting may serve as a novel mode of immunotherapy in disease.

Original languageAmerican English
Article number1003871
JournalFrontiers in Immunology
Volume13
DOIs
StatePublished - 5 Oct 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Völs, Kaisar-Iluz, Shaul, Ryvkin, Ashkenazy, Yehuda, Atamneh, Heinberg, Ben-David-Naim, Nadav, Hirsch, Mitesser, Salpeter, Dzikowski, Hayouka, Gershoni, Fridlender and Granot.

Keywords

  • inflammation
  • nanoparticles
  • neutrophil
  • reactive oxygen species
  • targeted delivery

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