期刊
MATERIALS
卷 12, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ma12244121
关键词
gold nanoparticles; stabilisation agent; cytotoxicity; immune response; cytokines
类别
资金
- Ministry of Education, Science and Technological Development of Serbia [ON 175102]
- Slovenian Research Agency [I0-0029]
- Medical Faculty of the Military Medical Academy, University of Defense in Belgrade [MFVMA 17-19/07]
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 mu g/mL), in contrast to PVP-GNPs, which were cytotoxic at higher concentrations. Control GNPs inhibited the production of IFN-Upsilon 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-alpha) and Th1-related cytokines (IFN-Upsilon 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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