Tantalum–Zirconium Co‐Doped Metal–Organic Frameworks Sequentially Sensitize Radio–Radiodynamic–Immunotherapy for Metastatic Osteosarcoma

Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) and antitumor immunity synchronously urgently needed. Here, the authors developed a nanoscale metal-organic framework (MOF, named TZM) by co-doping high-atomic elements Ta and Zr as metal nodes and porphyrinic molecules (tetrakis(4-carboxyphenyl)porphyrin (TCPP)) as a photosensitizing ligand. Given the 3D arrays of ultra-small heavy metals, porous TZM serves as an efficient attenuator absorbing X-ray energy and sensitizing hydroxyl radical generation for RT. Ta-Zr co-doping narrowed the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap and exhibited close energy levels between the singlet and triplet photoexcited states, facilitating TZM transfer energy to the photosensitizer TCPP to sensitize singlet oxygen (