Tumor-targeting attenuated Salmonella could induce certain antitumor therapeutic effect through its proliferation characteristic and the consequent activated immune response, while host defense cells represented by neutrophils would trap and eliminate these invading bacteria via producing excess hydrogen peroxide (H₂O₂)-including reactive oxygen species in the bacteria-infected tumor, thereby impairing the efficacy of the bacteria treatment of tumor. Herein, we attempt to combine bacteria treatment and oxygen-dependent radioimmunotherapy of tumor through injection of neutrophil-targeted nano-catalase into the bacteria-treated mice for perfect tumor treatment outcome. Denatured albumin is used to coat catalase and deliver it to the neutrophils infiltrated in bacteria-infected tumor tissue. Taking advantage of the generating H₂O₂ by neutrophils, easily-diffused oxygen is produced and spread the whole tumor under the catalysis of nano-enzyme, leading to enhanced radiotherapy of hypoxic tumor cells. Moreover, the optimized tumor microenvironment, synergistically caused by potent immune-stimulation of bacteria, generating oxygen and tumor radiotherapy, would boost the antitumor immunity. This novel combination therapy strategy holds great promise to provide new ideas for future clinical cancer treatment.

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Although there are a variety of treatments for RA, the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs (DMARD), which would induce obvious side-effect in patients after long-term administration. Herein, an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin nanomedicine. The hydrophobic drug methotrexate (MTX) could induce self-assembly of superoxide dismutase (SOD) and human serum albumin (HSA) to form HSA-SOD-MTX nanoparticle. After intravenous injection, dual-modal imaging including fluorescence imaging or single-photon emission computed tomography (SPECT)/CT imaging exhibits high accumulation of cyanine 5.5 (Cy5.5) or ¹²⁵I labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis (CIA) mice. Importantly, using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species (ROS) and MTX to suppress inflammation, HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other groups. Micro-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA- SOD-MTX nanoparticles is significantly relived, which was further demonstrated by the histological analysis and the inflammatory factors measurement. The synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side effects. Therefore, our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX, which may provide the reference for clinical RA treatment.

Local hypoxia in solid tumors often results in resistance to radiotherapy (RT), in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide (Au@MnO₂) core–shell nanoparticles with a polyethylene glycol (PEG) coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO₂ nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO₂ shell may trigger the decomposition of endogenous H₂O₂ in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO₂-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO₂-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.