Mesoporous Silica-Based Nanomotors for Stimuli-Responsive Tumor Penetration and Enhanced Photodynamic/Photothermal Synergistic Therapy

Photodynamic therapy (PDT), as a noninvasive tumor treatment strategy, relies on the light-triggered generation of reactive oxygen species (ROS) by photosensitizers, demonstrating significant clinical potential for solid tumor therapy. However, the hypoxic tumor microenvironment and the lack of autonomous motility in conventional nanocarriers often limit the oxygen-dependent ROS production capacity of photosensitizers. In this study, we designed a hydrogen peroxide (H2O2)-driven nanomotor system based on mesoporous silica surface-loaded with the photosensitizer zinc phthalocyanine (ZnPc). This nanomotor can specifically exploit the overexpressed H2O2 in the tumor microenvironment as a chemical fuel, generating O2 bubbles through catalytic decomposition to propel autonomous motion. This unique motility significantly enhances the penetration capability of the nanocarrier within solid tumor tissues. Meanwhile, the in situ produced O2 not only serves as a propulsion source but also effectively alleviates tumor hypoxia, providing sufficient oxygen for ZnPc-mediated PDT and substantially improving the ROS generation efficiency. The system innovatively establishes a synergistic therapeutic mechanism of motion-enhanced penetration, oxygen-supplemented therapy, and efficacy-feedback-driven propulsion, offering a strategy to overcome drug delivery barriers and hypoxia-induced resistance in solid tumor treatment.