Gold nanorods with spatial separation of TiO2 deposition for plasmonic effect and Schottky junction enhanced antioxidant stress and hydrogen therapy of rheumatoid arthritis

Hydrogen (H2) therapy is a new and effective approach for treatment of inflammation-related diseases. Nevertheless, the non-polarity and poor solubility of H2 under physiological status lead to its limited therapeutic effect. Here, we developed spatially separated Au/TiO2 nanodumbbells (NDs) as H2 generators and further conjugated them with Arg-Gly-Asp (RGD) peptides (labeled R-Au/TiO2) to achieve inflammatory joint targeting for precise treatment of rheumatoid arthritis (RA). The Au/TiO2 NDs structure combines the surface plasmon resonance (SPR) excitation of gold nanorods (Au NRs) and Schottky junction to exhibit very efficient photocatalytic H2 production under near-infrared light irradiation. In situ generated H2 gas acts as an active ingredient to scavenge reactive oxygen species (ROS) and clear inflammation. Through active H2 scavenging of ROS and inflammation, R-Au/TiO2 alleviated oxidative stress and reduced levels of inflammatory cytokines, showing considerable reduction in joint destruction and suppression of arthritis severity in a collagen-induced arthritis mouse model. Furthermore, the photothermal properties of R-Au/TiO2 nanoparticles (NPs) endow them with photothermal therapeutic effects, which synergize with the anti-inflammatory and anti-oxidative stress of H2, further enhancing the therapeutic effect. Therefore, R-Au/TiO2 NPs show great promise for treating RA and advancing clinical translation.