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Species differences in opsonization and phagocyte recognition of preclinical poly-2-alkyl-2-oxazoline-coated nanoparticles

Lookup NU author(s): Professor Moein MoghimiORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© The Author(s) 2025.Poly(ethylene glycol) (PEG) is widely used in nanomedicine design, but emerging PEG immunogenicity in the general population is of therapeutic concern. As alternative, polyoxazolines are gaining popularity, since “polyoxazolinated” nanoparticles show long-circulating properties comparable to PEGylated nanoparticles in mice. Here, we show species differences in opsonization and differential uptake by monocytes and macrophages of nanoparticles coated with either poly-2-methyl-2-oxazoline or poly-2-ethyl-2-oxazoline. These nanoparticles evade murine opsonization process and phagocytic uptake but porcine ficolin 2 (FCN2), through its S2 binding site, recognizes polyoxazolines, and mediates nanoparticle uptake exclusively by porcine monocytes. In human sera, FCN opsonization is isoform-dependent showing inter-individual variability but both FCN2 and complement opsonization promote nanoparticle uptake by human monocytes. However, nanoparticle uptake by human and porcine macrophages is complement-dependent. These findings advance mechanistic understanding of species differences in innate immune recognition of nanomaterials’ molecular patterns, and applicable to the selection and chemical design of polymers for engineering of the next generation of stealth nanoparticles.

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Author(s): Tavano R, Morillas-Becerril L, Geffner-Smith A, Ronzani G, Gervasutti R, Arrigoni G, Battisti I, Morbidelli M, Polverino de Laureto P, Palazzi L, Natale A, Schiavon E, Coin P, Benetti EM, Romio M, Corzana F, Jimenez-Moreno E, Sturlese M, Bolcato G, Moro S, Moghimi SM, Mancin F, Papini E

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2025

Volume: 16

Issue: 1

Online publication date: 18/03/2025

Acceptance date: 27/02/2025

Date deposited: 09/04/2025

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-025-57648-2

DOI: 10.1038/s41467-025-57648-2

PubMed id: 40102395

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