Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles / A. G. Pershina, O. Y. Brikunova, S. V. Vtorushin [et al.] // Nanomedicine: nanotechnology, biology and medicine. - 2021. - Vol. 32. - P102317 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): PH PROFILE -- ENDOCYTOSIS -- IRON OXIDE MAGNETIC NANOPARTICLES Аннотация: Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs. |
Peptide ligands on the PEGylated nanoparticle surface and human serum composition are key factors for the interaction between immune cells and nanoparticles / A. G. Pershina, A. M. Demin, N. A. Perekucha [et al.] // Colloids and Surfaces B: Biointerfaces. - 2023. - Vol. 221. - P112981 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: 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. |