Gold Nanoclusters Display Low Immunogenic Effect in Microglia Cells

Abstract

Gold nanoparticles hold a great promise for both clinical and preclinical applications. The major factors impeding such applications are toxicity of new nanomaterials including e.g., pro-apoptotic activities or inflammatory effects, but also their potential to accumulate in the body or inadequate absorption, distribution, metabolism and excretion (ADME) profiles. Since such adverse effects depend on the size, form and coating of nanomaterials, the search for new, less toxic nanomaterials with low tendency to accumulate is highly active domain of research. Here, we describe optical and biological properties of Au18 gold nanoclusters (NCs), small gold nanoparticles composed of 18 atoms of gold and stabilized with glutathione ligands. These nanoclusters may be suitable for in vivo applications owing to their low toxicity and biodistribution profile. Specifically, using lactate dehydrogenase (LDH) test in P19 cell line we found that Au18 NCs display low toxicity in vitro. Importantly, using primary microglial cells we showed that at low concentrations Au18 NCs display anti-inflammatory signaling on evidence of reduced interleukin 1-β (IL1-β) levels and unchanged levels of tumor necrosis factor (TNF-α) or Ym1/2. Such effect was dose dependent as higher concentrations of Au18 NCs induced expression of pro-inflammatory cytokines and suppression of anti-inflammatory cytokine Ym1/2, pointing, thus, to global inflammatory activity. Finally, we also showed that within 3 days Au18 NCs can be completely eliminated from the liver reported as the major target organ for accumulation of gold nanoparticles. These data point to a potential of gold nanoparticles for further biomedical studies.

Plasmonic Enhancement of Two-Photon Excited Luminescence of Gold Nanoclusters

“…Depending on the nanoclusters size and structure, it can be located from blue to near infrared (NIR), the most attractive region in terms of bioimaging applications. Recent studies on toxicity and biodistribution of Au 18 (SG) 14 in in vivo systems show promising results and are the first step to utilizing nanoclusters for bioimaging and biosensing applications [ 20 , 21 , 22 ]. Nanoclusters are well-characterised under one-photon excitation, but also present excellent nonlinear optical properties, which can be utilized in two-photon imaging [ 23 , 24 , 25 ].…”

Metal Nanoclusters as Biomaterials for Bioapplications: Atomic Precision as the Next Goal

“…Therefore, the synthesis of metal nanoclusters of different sizes is worthy of a systematic study in order to broaden their application scope. Similarly, as we discussed above, the surface chemistry of NCs also plays a crucial role in altering their properties and stability. − Further understanding of the fundamental principles underlying the tailoring of metal NCs to obtain excellent properties is required in future research. − …”

Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles

“…They consist of 18 atoms of gold and are stabilized with glutathione ligands. The authors of this study showed that these Au18 gold nanoclusters (NCs) have, at low concentrations, anti-inflammatory signaling (reduction of (IL1-β) levels, unchanged levels of TNF-α or Ym1/2) but, at higher concentrations, they can have pro-inflammatory activity [ 75 ]. The authors suggested that the presence of glutathione could be the source of this anti-inflammatory activity.…”