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Updated: Jun 29, 2026
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Tiopronin monolayer-protected silver nanoparticles modulate IL-6 secretion mediated by Toll-like receptor ligands
Paula M Castillo1, Juan L Herrera, Rafael Fernandez-Montesinos
1Department of Physical, Chemical & Natural Systems, Pablo de Olavide University, Seville, Spain.
Aims:
Capped silver nanoparticles that can be coupled to a variety of molecules and biomolecules are of great interest owing to their potential applications in biomedicine. However, there are no data about their toxicity or functional effects on a key innate immune response, such as IL-6 secretion, after the engagement of the main group of pathogen-associated molecular patterns receptors, that is, the Toll-like receptors (TLRs).
Materials & Methods:
N-(2-mercaptopropionyl)glycine (tiopronin)-capped silver (Ag@tiopronin) nanoparticles of a narrow sized distribution ( approximately 5 nm) were synthesized and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, Raman, (1)H-NMR and total correlation spectroscopy. Cytotoxicity was determined by lactate deshidrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium assays in Raw 264.7 macrophages. IL-6 was measured by ELISA.
Results & Discussion:
Ag@tiopronin nanoparticles have a narrow size distribution ( approximately 5 nm), high solubility and stability in aqueous environment with no cytotoxicity in terms of mitochondrial function or plasma-membrane integrity at concentrations as high as 200 microg/10(6) cells. Ag@tiopronin nanoparticles were not proinflammatory agents, but remarkably they specifically impaired the IL-6 secretion mediated by TLR2, TLR2/6, TLR3 or TLR9 stimulation in co-treatment experiments. However, in pretreatment experiments, nanoparticles enhanced the susceptibility of macrophages to inflammatory stimulation mediated by TLR2/1 and TLR2/6 specific ligands while severely impairing the IL-6 secretion activated by the TLR3 or TLR9 ligands.
Conclusions:
Contrary to what is found for bare silver nanoparticles, Ag@tiopronin nanoparticles are noncytotoxic to macrophages. Ag@tiopronin nanoparticles showed differential effects on TLR signaling of a high degree of specificity, without proinflammatory effects by themselves. These effects have to be borne in mind when using bioconjugates of Ag@tiopronin nanoparticles for future medical applications.
