Peptide ligands on the PEGylated nanoparticle surface and human serum composition are key factors for the interaction between immune cells and nanoparticles

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 221; p. 112981
• Main Authors: Pershina, Alexandra G., Demin, Alexander M., Perekucha, Natalya A., Brikunova, Olga Y., Efimova, Lina V., Nevskaya, Kseniya V., Vakhrushev, Alexander V., Zgoda, Victor G., Uimin, Mikhail A., Minin, Artem S., Malkeyeva, Dina, Kiseleva, Elena, Zima, Anastasia P., Krasnov, Victor P., Ogorodova, Ludmila M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2023
• Subjects: Iron oxide nanoparticles; Monocyte; PEG; PHLIP; Protein Corona; RGD; Protein Corona; PHLIP; PEG; Iron oxide nanoparticles; Monocyte; RGD
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2022.112981

The architecture of a nanoparticles’ surface formed due to a modification with a ligand and protein corona formation in biofluids is critical for interactions with cells in vivo. Here we studied interactions of immune cells with magnetic nanoparticles (MNPs) covalently modified with polyethylene glycol (PEG) and their counterparts conjugated with peptides: a pH (low) insertion peptide (pHLIP) and cycloRGD as a targeting ligand in human serum. The conjugation of MNPs-PEG with pHLIP, but not with cycloRGD, enhanced the association of these particles with mononuclear phagocytic cells in vitro and in vivo. We did not find a clear difference in protein corona composition between the pHLIP-modified and parental PEGylated nanoparticles. Analysis of the effect of autologous human serum on MNP uptake by monocytes showed that the efficiency of endocytosis varies among healthy donors and depends on intrinsic properties of serum. Nevertheless, using classic blood, coagulation, biochemical tests, and anti-PEG IgG serum level, we failed to identify the cause of the observed interdonor variation. These individual differences should be taken into consideration during testing of nanotherapeutics. [Display omitted] •Structure and density of a peptide on the nanoparticle surface is critical for the interactions with an immune cell.•Monocytes are the primary catchers of MNPs ex vivo and in vivo.•Uptake efficiency of MNPs by the monocytes demonstrates interdonor variation and depends on human serum composition.