NIR-II light-assisted radiotherapy based on ultrasmall HfO2-embedded porous carbon nanooctahedra for overcoming tumor radioresistance

Radiotherapy (RT) remains a prevalent method for malignant tumor treatment. However, high dosage of radiation is usually implemented in clinical due to the inherent radioresistance of tumors. Herein, a metal-organic framework (MOF)-derived porous carbon nanooctahedra embedded high-density ultrasmall hafnium oxide (HfO2) is first developed as a versatile nanosensitizer (HPCN) to improve the radiosensitivity. Pyrolysis of Hf-MOF under an inert atmosphere results in the transformation of Hf-cluster into uniformly distributed HfO2 and the organic linker directly converts into porous carbonaceous frameworks. The unique structure avoids the potential aggregation of HfO2 and provides more active sites to absorb/convert X-ray energy, improving the sensitivity of radiation. Notably, carbon substrate endows the nanosensitizer with excellent peroxidase-like activity and distinct NIR-II absorption properties, making it suitable for catalytic conversion of hydrogen peroxide and NIR-II photothermal therapy, which further render tumor cells increasingly susceptible to RT. In vitro and in vivo results demonstrated that the prepared nanosensitizer significantly improved RT efficacy at tumor site and reduced side-effect in normal tissues. We believe this work opens a new avenue for the exploration of MOF-derived radiosensitizers in clinical tumor treatment.