Metal–Organic Framework-Derived Multifunctional Nucleic Acid Nanoprobes for Hypoxia Imaging-Guided Radiosensitization

The efficacy of radiotherapy (RT) is usually restricted by the hypoxic microenvironment and the poor radiation attenuation coefficient of tumor tissue. Theranostic probes that simultaneously evaluate the hypoxia degree and sensitize cancer cells toward RT are promising for improving the treatment efficacy and avoiding overtreatment. We rationally designed a metal-organic framework (MOF)-derived multifunctional nanoprobe for hypoxia imaging-guided radiosensitization. Hf-MOF was carbonized to obtain a porous carbonous nanostructure containing ultrasmall HfO₂ (HfC); then, a fluorophore-labeled HIF-α mRNA antisense sequence was readily adsorbed and quenched by HfC to obtain the nanoprobe (termed HfC-Hy). The antisense sequence could easily hybridize with HIF-α mRNA and recover its fluorescence signal to evaluate the degree of hypoxia, while the HfC nanostructure could deposit more radiation energy in cancer cells for radiosensitization. A series of in vitro and in vivo experiments demonstrated that the nanoprobe could be successfully utilized for imaging the hypoxic degree of cancer cells/tumor tissue and guiding radiosensitization. This work not only developed a highly efficient and safe nanosensitizer but also offered a potential solution for customized clinical RT.