ZIF-8-inspired cascading nanoreactors for photodynamic/starvation synergistic therapy of breast cancer

The treatment of breast cancer (BC) faces multiple challenges, including high recurrence rates, drug resistance, and toxic side effects. This study constructed a cell membrane-mimicking biomimetic cascade nanoreactor, mCGH@ZIF, which is loaded with the photosensitizer chlorin e6 (Ce6), glucose oxidase (GOx), and hemin, enabling synergistic starvation-photodynamic therapy. Within the tumor microenvironment, GOx depleted glucose and generated H₂O₂; hemin converted H₂O₂ into O₂ in situ, effectively alleviated hypoxia and amplified the generation of Ce6-mediated singlet oxygen; and the cancer cell membrane coating enabled both immune evasion and homologous targeting. In vitro experiments demonstrated that mCGH@ZIF significantly suppressed 4T1 breast cancer cell proliferation while preserving excellent biocompatibility. This strategy established a closed-loop system integrating glucose depletion, oxygen production, and reactive oxygen species (ROS) generation, overcame the limitations of monotherapies, and offered a novel approach for precision combination therapy in breast cancer.