Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Buenteweg 17, 30559 Hannover, Germany.
Center for Systems Neuroscience, 30559 Hannover, Germany.
Int J Mol Sci. 2023 Jan 29;24(3):2565. doi: 10.3390/ijms24032565.
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.
纳米颗粒 (NPs) 在生物医学应用中的一个主要缺点是它们在免疫细胞中的优先吞噬作用,可以通过表面修饰如聚乙二醇化来避免。然而,对于不同聚乙二醇 (PEG) 链长对免疫细胞的能力以及可能的免疫毒性作用的研究仍然很少。因此,生成了原代小鼠巨噬细胞和树突状细胞,并将其与用不同 mPEG 链(2 kDa、5 kDa 和 10 kDa)修饰的磁性纳米多孔硅纳米颗粒 (MNPSNPs) 一起孵育。测定了细胞毒性、细胞因子释放和活性氧物质 (ROS) 的形成。检测了这两种细胞类型的免疫能力,并观察了 MNPSNPs 进入巨噬细胞的情况。高达 150 μg/mL 的 MNPSNPs 浓度对两种细胞类型的代谢活性或免疫能力均无影响。然而,与较大 PEG 链孵育的巨噬细胞中 ROS 显著增加,而细胞因子(TNF-α和 IL-6)的浓度并未表明存在炎症过程。对 MNPSNPs 摄取的研究表明,内化的起始和细胞内荧光强度没有差异。该研究没有表明 PEG 化 MNPSNPs 具有免疫毒性作用。然而,仍需要对其内化进行优化,以确保有效的药物递送。