Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro

Abstract

Engineering nanoparticles (NPs) for immune modulation require a thorough understanding of their interaction(s) with cells. Gold NPs (AuNPs) were coated with polyethylene glycol (PEG), polyvinyl alcohol (PVA) or a mixture of both with either positive or negative surface charge to investigate uptake and cell response in monocyte-derived dendritic cells (MDDCs). Inductively coupled plasma optical emission spectrometry and transmission electron microscopy were used to confirm the presence of Au inside MDDCs. Cell viability, (pro-)inflammatory responses, MDDC phenotype, activation markers, antigen uptake and processing were analyzed. Cell death was only observed for PVA-NH 2 AuNPs at the highest concentration. MDDCs internalize AuNPs, however, surface modification influenced uptake. Though limited uptake was observed for PEG-COOH AuNPs, a significant tumor necrosis factor-alpha release was induced. In contrast, (PEG + PVA)-NH 2 and PVA-NH 2 AuNPs were internalized to a higher extent and caused interleukin-1beta secretion. None of the AuNPs caused changes in MDDC phenotype, activation or immunological properties.

Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model

“…13 After PVA-NH 2 AuNP exposure corresponding to 3.44 ± 0.36 μg/cm 2 of deposited Au in the insets, the cells showed increased late apoptotic levels compared to the negative control. The apoptosis levels of the PVA-COOH AuNP-treated cells were similar to those of the negative control.…”

“…15,49 Briefly, adenocarcinoma human alveolar basal epithelial cells (A549 cells) were grown under submerged conditions for 5 days on cell culture inserts (surface area of 4.2 cm 2 , pores with 3.0 μm diameter, high pore density PET membranes for six-well plates (BD Biosciences, Basel, Switzerland; 353502) at a density of 1 × 10 6 cells/mL). Monocytes were isolated from human buffy coat from healthy volunteers (Blood Donation Service, Bern University Hospital, Bern, Switzerland) by gradient centrifugation (Lymphoprep, Axis Scield, Oslo, Norway) as previously described by Blank et al 9 and Fytianos et al 13 Monocytes were differentiated into MDDCs by adding 10 ng/mL granulocyte−monocyte−colony stimulating factor and 10 ng/mL IL-4. MDMs were differentiated by adding 10 ng/mL monocyte−colony stimulating factor.…”

“…Using this NP library, we have shown that surface modification can alter cellular uptake, with the PVA-NH 2 and PVA-COOH AuNPs being taken up by human blood monocyte-derived dendritic cells (MDDCs) in vitro, while functional and immunological properties were not impaired at concentrations of 20 μg/mL. 13,14 In this study, we have further explored the potential of aerosolized PVA-COOH and PVA-NH 2 AuNPs in terms of their cellular uptake and functional and immunological properties in an advanced in vitro coculture cell model representing the human lung epithelial tissue barrier 15 under realistic exposure scenarios, that is, exposure of the AuNPs as an aerosol over the lung cell surface. Furthermore, the ability of DC-SIGN-conjugated AuNPs to specifically target MDDCs in the coculture model was investigated.…”

Nanoparticles and direct immunosuppression

“…57 Alternatively, other polymer and organic coatings did not produce comparable anti-inflammatory responses. [58][59][60] This suggests the size and coating either perform in unison or direct different pathways that induce the immunosuppressive response. Decoupling of these mechanisms would provide a clear direction to engineer better gold-based nanomedicines with the ability to regulate the IL-1b pathways for the treatment of chronic rheumatic disease.…”

Maturation of dendritic cells in vitro and immunological enhancement of mice in vivo by pachyman- and/or OVA-encapsulated poly(D,L-lactic acid) nanospheres

“…After transferring to the draining lymph nodes (DLNs) and submitting pieces of antigen to T-lymphocytes with high expression levels of adhesion and co-stimulatory molecules, major histocompatibility complex (MHC) class I and II proteins, and secretion of inflammatory cytokines, 18 DCs activate T cells, thereby initiating and regulating Th1 and Th2 immune responses. 19,20 The phagocytosis of PLA micro-and nanoparticles by murine bone marrow-derived cells has previously been demonstrated in vitro. 21 Similarly, there is evidence that particles can accelerate antigen uptake by APCs and promote antigen presentation to T cells, thereby eliciting potent cellular and humoral immune responses.…”