TY - JOUR

T1 - Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells

AU - Storjohann, Ronja

AU - Gericke, Birthe

AU - Reifenrath, Janin

AU - Herrmann, Timo

AU - Behrens, Peter

AU - Oltmanns, Hilke

AU - Meißner, Jessica

N1 - Funding Information: This study was supported by the project “Implant-Directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections” (project number: 280642759), which was funded by Deutsche Forschungsgemeinschaft (DFG), grant number: KI 361/6-2; JR, JB. This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation.

PY - 2023/1/29

Y1 - 2023/1/29

N2 - A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

AB - A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

KW - biocompatibility

KW - FeO

KW - immunotoxicology

KW - nanoporous silica nanoparticles

KW - phagocytosis

KW - superparamagnetic iron oxide nanoparticles

KW - targeted drug delivery

UR - http://www.scopus.com/inward/record.url?scp=85147895122&partnerID=8YFLogxK

U2 - 10.3390/ijms24032565

DO - 10.3390/ijms24032565

M3 - Article

C2 - 36768890

AN - SCOPUS:85147895122

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 3

M1 - 2565

ER -