Species differences in opsonization and phagocyte recognition of preclinical poly-2-alkyl-2-oxazoline-coated nanoparticles
Regina Tavano, Lucía Morillas-Becerril, Alessandra Geffner-Smith, G. Ronzani, R. Gervasutti, Giorgio Arrigoni, Ilaria Battisti, M. Morbidelli, Patrizia Polverino de Laureto, Luana Palazzi, Alda Natale, Eliana Schiavon, Patrizio Coin, Edmondo M. Benetti, Matteo Romio, Francisco Corzana, Ester Jiménez‐Moreno, Mattia Sturlese, Giovanni Bolcato, Stefano Moro, S. Moein Moghimi, Fabrizio Mancin, Emanuele Papini
Abstract
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. Species differences in innate immune sensing could impact nanomedicine development. Here the authors examine phagocyte recognition and show the defined molecular patterns on polymer-coated nanoparticles in different species are driven by ficolin and complement opsonisation.