Effects of PVA coated nanoparticles on human immune cells

Abstract

Nanotechnology provides new opportunities in human medicine, mainly for diagnostic and therapeutic purposes. The autoimmune disease rheumatoid arthritis (RA) is often diagnosed after irreversible joint structural damage has occurred. There is an urgent need for a very early diagnosis of RA, which can be achieved by more sensitive imaging methods. Superparamagnetic iron oxide nanoparticles (SPION) are already used in medicine and therefore represent a promising tool for early diagnosis of RA. The focus of our work was to investigate any potentially negative effects resulting from the interactions of newly developed amino-functionalized amino-polyvinyl alcohol coated (a-PVA) SPION (a-PVA-SPION), that are used for imaging, with human immune cells. We analyzed the influence of a-PVA-SPION with regard to cell survival and cell activation in human whole blood in general, and in human monocytes and macrophages representative of professional phagocytes, using flow cytometry, multiplex suspension array, and transmission electron microscopy. We found no effect of a-PVA-SPION on the viability of human immune cells, but cytokine secretion was affected. We further demonstrated that the percentage of viable macrophages increased on exposure to a-PVA-SPION. This effect was even stronger when a-PVA-SPION were added very early in the differentiation process. Additionally, transmission electron microscopy analysis revealed that both monocytes and macrophages are able to endocytose a-PVA-SPION. Our findings demonstrate an interaction between human immune cells and a-PVA-SPION which needs to be taken into account when considering the use of a-PVA-SPION in human medicine.

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

“…11 Moreover, non-coated and polyacrylic acid-coated IONPs induced IL-1β, IL-8, IL-6, TNF and IL-10 in primary human blood cells 12 and aminopolyvinyl alcohol-coated SPION increased the secretion of IL-1β, IL-4, IL-8, IL-6, MIP-1β and RANTES in whole blood samples. 13 In contrast, we did not observe pro-inflammatory cytokine production by IONPs in primary human monocytes, 14 which might be due to different properties of the IONPs and different cell types used.…”

Modification of the surface of superparamagnetic iron oxide nanoparticles to enable their safe application in humans

“…Cell pellets were then washed with phosphate-buffered saline (PBS) and nonspecific binding was blocked by preincubation with human immunoglobulin (5 mg/mL) for 10 minutes at 4°C. 25 After washing the cells with PBS, an antibody-mix (anti-CD3, anti-CD14, anti-CD19, and anti-CD15; all antibodies diluted 1/50 in PBS) was added, mixed, and the samples were incubated for 15 minutes at 4°C in the dark. Cells were washed twice and Annexin V-PE/7-AAD staining was performed according to the manufacturer's instructions.…”

“…Previously, we showed that amino (a)-PVA-SPION do not affect the survival 25 or activity 30 of human immune cells; however, these particles do cause unwanted immune reactions, in terms of increased cytokine secretion. 25 To enable safe medical application of these NP, modification of a-PVA-SPION is necessary.…”

“…Previously, we showed that amino (a)-PVA-SPION do not affect the survival 25 or activity 30 of human immune cells; however, these particles do cause unwanted immune reactions, in terms of increased cytokine secretion. 25 To enable safe medical application of these NP, modification of a-PVA-SPION is necessary. Because the coating of these NP was not optimally controlled in former experiments, it was not clear if the effects observed were due to the coated SPION themselves or to free-floating PVA polymer, which could trigger an immune reaction.…”

“…21 Furthermore, SPION are endocytosed by cells, particularly immune cells such as monocytes and macrophages, which are dedicated phagocytes that migrate into inflamed tissues. [22][23][24][25] SPION can be further functionalized by surface coating using proteins, peptides, antibodies, polymers, carbohydrates, aptamers, DNA, RNA, or oligosaccharides. 17 The composition and characteristics of the SPION surface have a strong influence on their stability, distribution, and biocompatibility, with regard to cellular uptake and cytotoxicity.…”