Photogenerated electrons from CeO2 via upconversion of excitons to conduction band enhanced photocatalysis for Photo-Therapy of Rheumatoid arthritis

• Pt-UCNP@CeO 2 nanoparticles for Rheumatoid arthritis (RA) are developed. • Pt-UCNP@CeO 2 nanoparticles relieve RA hypoxic microenvironment and inhibit angiogenesis. • FLS cells are died by physical damage mechanism via photodynamic therapy (PDT). • UCNPs can convert near infrared light (NIR) into Vis or UV to achieve PDT in deep tissue. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint hypoxia and synovial cell proliferation. Therefore, relieving hypoxia and removing synovial cells will be a new direction in the treatment of RA. Vasoactive intestinal peptide-loaded upconversion nanoparticles (UCNPs)@SiO 2 @Pt@CeO 2 (V-USPC) were used for in situ oxygen (O 2 ) production/photothermal/photodynamic treatment of RA. On the one hand, under the irradiation of NIR laser, the optical transition of UCNPs triggers CeO 2 to form electron hole pairs which catalyze H 2 O to produce reactive oxygen species to achieve photodynamic therapy (PDT) which inhibit the proliferation of fibroblast-like synovial (FLS) cells. On the other hand, Pt-mediated photothermal therapy also has a certain effect on the removal of proliferative FLS cells. In addition, the catalase activity of CeO 2 can catalyze the high level of H 2 O 2 in hypoxia environment to achieve in situ O 2 production which can alleviate hypoxia and resist angiogenesis. It is worth noting that the RA was improved by the synergistic action of PDT and PTT, and the generation of oxygen can alleviate RA hypoxia, which is a means to improve PDT. Therefore, the V-USPC NPs shows great potential in improving the therapeutic effect of RA.