Phase-transition engineered semi-metallic Cu₃PdN for photothermal-enhanced cuproptosis-induced cancer therapy

In-situ activation of cuproptosis shows considerable promise in cancer therapy. However, its efficacy is often hindered by the accumulation of copper ions and limitations of the activation strategy. Herein, a novel copper-palladium nitride (Cu₃PdN)-modified injectable hydrogel with enhanced photothermal conversion efficiency was designed to improve copper accumulation at tumor sites and achieve photothermia-enhanced cuproptosis. A phase transition from Cu₃N to Pd-doped Cu₃PdN was achieved, transforming the material from a semiconductor to a semi-metal with a reduced band gap. This modification endowed Cu₃PdN with full-spectrum absorption and enhanced photothermal conversion efficiency. Coupled with the abundant copper content, Cu₃PdN nanoparticles hold great potential for photothermal-enhanced, in-situ cuproptosis-based cancer therapy. The Cu₃PdN system demonstrates stimulus-responsive Cu(I) ions release and Fenton-like activity, promoting the generation of reactive oxygen species, mitochondrial dysfunction, and the oligomerization of dihydrolipoamide S-acetyltransferase, which together trigger cuproptosis. Overall, this study provides a promising approach for utilizing metal nitrides to induce photothermal-enhanced cuproptosis in tumor therapy.