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

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 PtAu2 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

PtAu2 clusters exhibited satisfactory biocompatibility and cellular uptake behavior, with potent anti-inflammatory and anti-OC activities in vitro. In addition, PtAu2 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.