A multifunctional mesoporous silica drug delivery nanosystem that ameliorates tumor hypoxia and increases radiotherapy efficacy.

Radiotherapy (RT) is a widely used treatment with strong therapeutic effects, but overcoming challenges related to hypoxia-induced tumor resistance and ineffective antitumor immune responses is crucial for optimal outcomes. In this study, we developed a versatile nanosystem using mesoporous silica nanoparticles (MSNs), R837, and a small quantity of manganese peroxide (Mn/ZnO₂). The synthesized MSN@R837-Mn/ZnO₂ nanoparticles exhibited precise tumor targeting and accumulation, controlled drug release under acidic conditions, and increased sensitivity in magnetic resonance imaging. These attributes collectively augmented the therapeutic efficacy of RT by alleviating hypoxia and immunosuppression. Tumor cells treated with RT combined with these nanoparticles displayed reduced oxidative stress, alleviated hypoxia, and normalized blood vessel formation. Notably, all mice in the RT + PD-1 + MSN@R837-Mn/ZnO₂ group achieved complete tumor regression with extended survival. Safety assessments confirmed the absence of MSN@R837-Mn/ZnO₂ toxicity, highlighting its potential as a promising approach with dual functionality for the diagnostic imaging and treatment of cancer. Radiotherapy (RT) faces challenges like hypoxia-induced tumor resistance and weak antitumor immune responses. This study developed a nanosystem using mesoporous silica nanoparticles (MSNs), R837, and manganese peroxide (Mn/ZnO₂). The MSN@R837-Mn/ZnO₂ nanoparticles showed precise tumor targeting, controlled drug release in acidic conditions, and enhanced MRI sensitivity, boosting RT efficacy by reducing hypoxia and immunosuppression. Tumor cells treated with RT and these nanoparticles had less oxidative stress, improved hypoxia, and normalized blood vessels. Remarkably, all mice in the RT+PD-1+MSN@R837-Mn/ZnO₂ group achieved complete tumor regression and extended survival, with no toxicity observed, indicating its potential for cancer imaging and treatment. [ABSTRACT FROM AUTHOR]