Ultrasmall PtAu₂ nanoclusters activate endogenous anti-inflammatory and anti-oxidative systems to prevent inflammatory osteolysis

Abstract

Rationale: Inflammatory osteolysis, characterized by abundant immune cell infiltration and osteoclast (OC) formation, is a common complication induced by bacterial products and/or wear particles at the bone-prosthesis interface that severely reduces long-term stability after implantation. Molecular nanoclusters are ultrasmall particles with unique physicochemical and biological properties that have great potential as theranostic agents for treating inflammatory diseases. Methods: In this study, heterometallic PtAu 2 nanoclusters with sensitive nitric oxide-responsive phosphorescence turn-on characteristics and strong binding interactions with cysteine were designed, making them desirable candidates for the treatment of inflammatory osteolysis. Results: PtAu 2 clusters exhibited satisfactory biocompatibility and cellular uptake behavior, with potent anti-inflammatory and anti-OC activities in vitro . In addition, PtAu 2 clusters alleviated lipopolysaccharide-induced calvarial osteolysis in vivo and activated nuclear factor erythroid 2-related factor 2 (Nrf2) expression by disrupting its association with Kelch-like ECH-associated protein 1 (Keap1), thereby upregulating the expression of endogenous anti-inflammatory and anti-oxidative products. Conclusion: Through the rational design of novel heterometallic nanoclusters that activate the endogenous anti-inflammatory system, this study provides new insights into the development of multifunctional molecular therapeutic agents for inflammatory osteolysis and other inflammatory diseases.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

“…In this manuscript, we introduced H 2 O 2 to realize oxidative stress. The introduction of H 2 O 2 significantly promoted the expression of macrophage inflammatory factors, which was consistent with the results of Chen, but the molecular mechanism was different [ 53 ]. In Chen’s work, PtAu 2 nanoclusters activated nuclear factor erythroid 2-related factor 2 (Nrf2) expression by disrupting its association with Kelch-like ECH-associated protein 1 (Keap1), thereby upregulating the expression of endogenous anti-inflammatory and anti-oxidative products.…”

“…H 2 O 2 was used to simulate oxidative stress according to Zhang and Cheng [ 51 , 52 ]. In Geng and Chen’s study, high concentrations of glucose and LPS were used to induce cellular oxidative stress, respectively [ 22 , 53 ]. In this manuscript, we introduced H 2 O 2 to realize oxidative stress.…”

Hydroxytyrosol Alleviates Intestinal Oxidative Stress by Regulating Bile Acid Metabolism in a Piglet Model

“…Oxidative stress not only triggers inflammatory responses, but the sustained presence of inflammation can also exacerbate oxidative stress, forming a vicious cycle that causes further damage to cells and tissues [ 44 , 45 ]. Cytokines such as tumor necrosis factor (TNF-α), interleukins (IL-1β, IL-6), and others play crucial roles in the inflammatory response by promoting cellular damage and the inflammatory process, thereby exacerbating oxidative stress.…”

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.…”