Peptide-Protected Gold Nanoclusters Efficiently Ameliorate Acute Contact Dermatitis and Psoriasis via Repressing the TNF-α/NF-κB/IL-17A Axis in Keratinocytes

Abstract

Immune-mediated skin diseases have a high prevalence and seriously affect patients’ quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Gold nanoclusters fabricated by using peptides (pep-AuNCs) have appeared as potential biomedical nanomaterials because of their excellent biocompatibility, ease of fabrication and unique physicochemical properties. Glutathione (GSH) is an endogenous tripeptide and has been used for lightening the skin color. Therefore, we fabricated a well-defined gold nanocluster with GSH as an example to explore the immunomodulatory effect of AuNCs on a TNF-α-treated human keratinocyte cell line (HaCaT) in vitro, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis (ICD) model and the oxazolone (OXA)-induced psoriatic model in vivo. The results indicated that topically applied AuNCs successfully attenuated the severity of ICD and psoriasis-like lesions. In vitro and in vivo, AuNCs effectively inhibited the abnormal activation of the NF-κB pathway and the consequent overexpression of proinflammatory cytokines in keratinocytes. In particular, the transactivation of IL-17A, the most important cytokine in psoriasis pathology, was effectively inhibited by AuNCs treatment. In addition, AuNCs did not show any obvious cytotoxicity in HaCaT cells at doses even up to 100 µM and did not induce any irritation in the healthy skin and major organs, which indicated their favorable biosafety. These results indicate that biocompatible pep-AuNCs might be a promising gold-based nanomedicine for the treatment of inflammatory skin diseases.

Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis via Nrf2-Dependent Macrophage Reprogramming

“…None of these tissues showed obvious damage (Supplementary Figure 9). These results, combined with our previous studies and others, extensively prove the biosafety of GA. − In summary, this Au nanocluster possessed excellent biosafety and potential to be used as a nanomedicine for treating both acute IBD and CAC.…”

Multiscale Bioresponses of Metal Nanoclusters

“…Intriguingly, metal NCs inhibit lipopolysaccharide (LPS)-induced inflammatory responses in macrophages by hindering the NF-𝜅B signaling pathway. [158,[164][165][166][167] These metal NCs can effectively suppress the LPS-induced heightened expression of pro-inflammatory cytokines, such as tumor necrosis factor-𝛼 (TNF-𝛼), IL-1𝛽, IL-6, inducible nitric oxide synthase (iNOS, i.e., nitric oxide, NO), and cyclooxygenase-2 (COX-2, i.e., prostaglandins, PEG 2 ). [158] Specifically in neuroinflammatory scenarios, metal NCs significantly boost the expression of heme oxygenase (an anti-inflammatory enzyme) in neuronal cells, thereby aiding in the protection of dopaminergic neurons.…”

The roles of templates consisting of amino acids in the synthesis and application of gold nanoclusters

“…197 GSH–AuNCs can efficiently ameliorate acute contact dermatitis and psoriasis via repressing the TNF-α/NF-κB/IL-17A axis in keratinocytes. 198 GSH–AuNCs modified by two amphiphilic peptides (P1 and P2) bound with negatively charged DSPE–PEG2000–COOH to form aggregates. After lysosomal escape, the highly stable AuNCs with good antitumor effect and biosafety were dissociated from intracellular aggregates and attached to the endoplasmic reticulum (ER), achieving the mutual promotion of autophagy and apoptosis in liver tumor cells.…”