Designing Bimetallic Metal-Organic Framework-Based Heterojunction Radiosensitizer for Enhanced Radiodynamic Therapy and Immunotherapy

Radiotherapy, as one of the most common strategies for clinical cancer treatment, suffers from failure due to the hypoxia, inflammation, and radiosensitivity difference of malignant tumors, side effects, and radioresistance. Heterojunction-based radiosensitizers attract great attention to the lower excitation energy and remarkable catalytic activity as compared to typical transition metal radiosensitizers. However, the bio-application of heterojunction radiosensitizers is in its infancy due to the challenges in structure engineering, rational energy band alignment, and ideal photogenerated carrier migration. Herein, a bimetallic metal-organic framework (MOF)-based heterojunction radiosensitizer is reasonably designed to enhance the radiodynamic therapeutic efficiency of Ru complex, and to activate natural killer (NK) cell-mediated innate immune responses for promoted tumor immunotherapy. This study not only designs a novel bimetallic MOF-based heterojunction structure but also elucidates the underlying action mechanisms in inhibiting cancer proliferation, which sheds light on the practicable design of radiosensitizers and the tumor combination treatment. A bimetallic metal-organic framework-based heterojunction radiosensitizer has been rationally designed to convert X-ray energy into photoelectron to improve radiodynamic therapeutic efficiency and to activate NK cells-mediated innate immune response, thus realizing enhanced radio-/immunotherapy.image