Doping-engineered PdRu bimetallic nanoalloys with nitric oxide delivery for synergetic photodynamic therapy

Photodynamic therapy (PDT) is often constrained by the insufficient therapeutic effect of reactive oxygen species (ROS) and poor stability of photosensitizers. To address these challenges, PdRu bimetallic nanoalloys (PdRu@PL) loaded with L-arginine (L-arg) as a nitric oxide (NO) donor were developed for synergistic PDT. A series of distinct morphologies-nanospheres, nanoflowers, and nanosheets-were synthesized, with the highly stable and uniformly alloyed PdRu NPs selected for further functionalization <i>via</i> PEGylation and L-arg loading. Under 808 nm laser irradiation, the PdRu nanoalloys exhibit excellent photothermal properties and generate ROS, including singlet oxygen and superoxide anions (˙O₂^-). The produced ˙O₂^- reacts with NO released from L-arg, forming highly cytotoxic peroxynitrite, a reactive nitrogen species. This cascade is further enhanced by catalase-like activities of the nanoalloys, which modulate the tumor microenvironment by decomposing hydrogen peroxide and alleviating hypoxia. <i>In vitro</i> experiments demonstrated efficient cellular uptake, concentration-dependent cytotoxicity against 4T1 cancer cells, and significant induction of apoptosis under laser exposure. <i>In vivo</i> studies in 4T1 tumor-bearing mice confirmed effective tumor accumulation of PdRu@PL, leading to nearly complete tumor ablation following treatment, without evident systemic toxicity. This work highlights PdRu bimetallic nanoalloys as a promising multifunctional platform for synergistic photodynamic and NO-based gas therapy, offering a strategy for enhanced anticancer efficacy.