Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor recurrence. Herein, we designed folic acid modified enzyme-like hafnium-based manganoporphyrin metal–organic framework nanoparticles (MnTCPP–Hf–FA MOF NPs) to overcome hypoxia-induced radioresistance and prevent postoperative recurrence. Hf, a high-Z element, can effectively absorb X-ray energy and convert O₂ and H₂O into reactive oxygen species to induce cell apoptosis. The MnTCPP ligand has an enzyme-like ability to catalytically decompose endogenous H₂O₂ into O₂ for enhancing RT in hypoxic tumors. In vivo experiments revealed that the MOF NPs could effectively inhibit melanoma growth and prevent tumor postoperative recurrence with only one X-ray irradiation after intravenous injection. We expect that the current study provides a versatile approach for solving the critical radioresistance issue of hypoxic tumors.

Covalent organic frameworks (COFs) have emerged as a kind of promising material for analytical and biomedical purposes. However, simultaneous cancer diagnosis and therapy with COFs remain a challenge. We report here a COF-based theranostic nanoplatform by integrating a dye-labeled oligonucleotide onto porphyrin-based COF nanoparticles for highly efficient cancer diagnosis and therapy. The fluorescence of the dye was effectively quenched by the COF through fluorescence resonance energy transfer (FRET). In the presence of biomarker survivin mRNA, more stable duplexes were formed and separated from the COF NPs, enabling the recovery of the fluorescence signal and selective cancer imaging. Under NIR laser irradiation, COF NPs generated abundant reactive oxygen species (ROS) to induce cancer cell apoptosis owing to their crystalline reticular structure. In vitro and in vivo experiments revealed that the nanoplatform has a high specificity and inhibition effect toward cancer cells and solid tumors. Interestingly, prognostic evaluation was also realized with COF-survivin. This work will offer new insights into COF-based probes and inspire the development of more versatile tools for biomedical applications.

Radiation therapy (RT) has been widely used for malignant tumor treatment. However, the large dosage of ionizing radiation and high frequency of radiotherapy in clinical cancer therapy cause severe damage to normal tissues adjacent to tumors. Therefore, how to increase the local treatment efficacy and reduce the damage to normal tissues has been a challenge for RT. Herein, we developed a novel strategy for enhanced RT based on a mitochondria targeted titanium dioxide-gold nanoradiosensitizer. When irradiated with X-rays, the nanosensitizer could produce reactive oxygen species (ROS) in the mitochondria, which induced the domino effect on the ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. A colony formation assay indicated that the cell survival rate when incubated with the mitochondrial targeted nanosensitizer was significantly lower than that of non-targeted groups. As demonstrated by in vivo experiments, the tumor was significantly suppressed even just once RT with the nanosensitizer.