Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells

Čolić, Miodrag; Džopalić, Tanja; Tomić, Sergej; Rajković, Jovana; Rudolf, Rebeka; Vuković, Goran D.; Marinković, Aleksandar D.; Uskoković, Petar S.

doi:10.1016/j.carbon.2013.09.090

Cited by 22 publications

(15 citation statements)

References 66 publications

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“…Such localization could improve the GNPs-mediated delivery of endosomal TLR agonists into DCs, such as CpG [11] or 7-thia-8-oxoguanosine [53]. However, we also found GNPs outside the endosomes, especially the smaller ones.…”

Section: Discussionmentioning

confidence: 62%

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

et al. 2014

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Gold nanoparticles (GNPs) are claimed as outstanding biomedical tools for cancer diagnostics and photo-thermal therapy, but without enough evidence on their potentially adverse immunological effects. Using a model of human dendritic cells (DCs), we showed that 10 nm- and 50 nm-sized GNPs (GNP10 and GNP50, respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP10 was more prominent. However, GNP10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP50 promoted Th17 polarization. Such effects of GNP10 correlated with a stronger inhibition of LPS-induced changes in Ca2+ oscillations, their higher number per DC, and more frequent extra-endosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP10 inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs' capacity to induce T cell-mediated anti-tumor cytotoxicity in vitro. Therefore, GNP10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP50.

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Section: Discussionmentioning

confidence: 62%

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

et al. 2014

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“…The slides were analysed using a light microscope (Nikon Eclipse 5i equipped with a Nikon DXM1200C Camera, Tokyo, Japan). The amount of internalised GNPs was assessed in a semiquantitative manner within the monocytes population of PBMNCs, by scoring individual cells from 0 to 4, as described previously [34]. The results are presented as a mean of uptake from three independent experiments.…”

Section: Internalisation Of Gnpsmentioning

confidence: 99%

The Effect of Stabilisation Agents on the Immunomodulatory Properties of Gold Nanoparticles Obtained by Ultrasonic Spray Pyrolysis

et al. 2019

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Gold nanoparticles (GNPs) have been investigated extensively as drug carriers in tumour immunotherapy in combination with photothermal therapy. For this purpose, GNPs should be stabilised in biological fluids. The goal of this study was to examine how stabilisation agents influence cytotoxicity and immune response in vitro. Spherical GNPs, 20 nm in size, were prepared by ultrasonic spray pyrolysis (USP). Three types of stabilising agents were used: sodium citrate (SC), polyvinyl-pyrrolidone (PVP), and poly-ethylene glycol (PEG). Pristine, non-stabilised GNPs were used as a control. The culture models were mouse L929 cells, B16F10 melanoma cells and human peripheral blood mononuclear cells (PBMNCs), obtained from healthy donors. Control SC- and PEG-GNPs were non-cytotoxic at concentrations (range 1–100 µg/mL), in contrast to PVP-GNPs, which were cytotoxic at higher concentrations. Control GNPs inhibited the production of IFN-ϒ slightly, and augmented the production of IL-10 by PHA-stimulated PBMNC cultures. PEG-GNPs inhibited the production of pro-inflammatory cytokines (IL-1, IL-6, IL-8, TNF-α) and Th1-related cytokines (IFN-ϒ and IL-12p70), and increased the production of Th2 cytokines (IL-4 and IL-5). SC-PEG inhibited the production of IL-8 and IL-17A. In contrast, PVP-GNPs stimulated the production of pro-inflammatory cytokines, Th1 cytokines, and IL-17A, but also IL-10. When uptake of GNPs by monocytes/macrophages in PBMNC cultures was analysed, the ingestion of PEG- GNPs was significantly lower compared to SC- and PVP-GNPs. In conclusion, stabilisation agents modulate biocompatibility and immune response significantly, so their adequate choice for preparation of GNPs is an important factor when considering the use of GNPs for application in vivo.

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“…In another study, a selective endosomal TLR7 agonist (7-thia-8-oxoguanosine, 7-TOG) was covalently attached to previously oxidized MWNTs, and tested for the ability to activate human monocyte-derived DCs. Efficient phagocytosis of the 7-TOG-MWCNT conjugate by DCs was achieved, as well as consequent delivery of the TLR7 agonist to endosomes [83]. Oxidized MWNTs have also been used as delivery system to carry melanoma antigen and CpG ODN adjuvant to DCs and potentiate effective humoral and cellular anti-tumor immunity [84].…”

Section: Carbon Nanotubesmentioning

confidence: 99%

Targeting Pattern Recognition Receptors (PRRs) in Nano- Adjuvants: Current Perspectives

Haghparast

Zakeri²,

Ebrahimian³

et al. 2016

CBNT

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Enormous progress in the field of vaccine development has moved the area from traditional vaccines using whole microorganisms to subunit vaccines containing only purified or modified antigenic proteins. The low immunogenic potentials of subunit vaccines compared to live attenuated pathogens, have prompted the research towards developing new adjuvants with the ability to mimic and enhance the innate and adaptive immune responses. Novel adjuvants formulations based on the discovery of pattern recognition receptors (PRRs), the main class of innate immunity sensors have recently gained interest. The major family of PRRs called Toll-like receptors (TLRs), which are expressed by a variety of cells and capable to induce innate immune responses and effective stimulation of transition from innate immune responses to adaptive immune responses. PRR ligands of natural and synthetic origin have been evaluated as potential adjuvants in a variety of applications including vaccine formulations. Apart from this, for generating effective and protective immune responses, targeted delivery of vaccine antigens along with PRR agonists to the desired cells is of great importance. New strategy of delivering vaccine antigens along with adjuvants using proper nano-sized materials has gained much attention during the recent years. Here we review the recent advances regarding PRR-based nano-adjuvants developments, focusing on current nano-materials based delivery system and their applications in biomedical sciences.

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Immunomodulatory effects of carbon nanotubes functionalized with a Toll-like receptor 7 agonist on human dendritic cells

Cited by 22 publications

References 66 publications

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

The Effect of Stabilisation Agents on the Immunomodulatory Properties of Gold Nanoparticles Obtained by Ultrasonic Spray Pyrolysis

Targeting Pattern Recognition Receptors (PRRs) in Nano- Adjuvants: Current Perspectives

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