Hafnium-Doped Prussian Blue Nanoparticles with Homologous Tumor Targeting and Magnetic Resonance Imaging Ability for Enhanced Tumor Radiotherapy via Photothermal Therapy and Hypoxia Relief

Radiotherapy (RT) continues to encounter significant obstacles such as formidable resistance, potential harm to adjacent healthy cells, and restricted effectiveness against tumors, resulting in a notable recurrence rate. Therefore, combining imaging, other treatments, and suitable enzyme activity in one nanoplatform can enhance the RT effect and reduce the damage to normal tissue. In this study, integrating hafnium in Prussian blue (PB) nanoparticles (PB NPs) provided innovative hafnium-doped PB (HPB) NPs as multifunctional radiosensitizers. The HPB NPs were enveloped by the cancer cell membrane, resulting in cancer cell membrane-camouflaged HPB (CMHPB) NPs that can specifically target homologous tumors. Moreover, owing to the inherent ability of photothermal therapy (PTT), magnetic resonance imaging (MRI), and catalase (CAT)-like activity of PB NPs, CMHPB NPs effectively overcome tumor hypoxia and realize the MRI-guided combined RT and PTT. The prepared HPB NPs possessed uniform and cubic morphology with a monodisperse size of approximately 80 nm and <i>T</i>₁ MRI capability (<i>r</i>₁ = 0.9309 mM^-1 S^-1). The HPB NPs showed reliable PTT efficiency and CAT-like activity in vitro and in vivo. Guided by MRI, the CMHPB NPs can be precisely delivered to the tumor region for combined RT and PTT for targeted destruction of tumor cells, significantly inhibiting tumor growth. The innovative multifunctional CMHPB NPs can be used for MRI-guided RT and PTT, which address the key challenges of RT and provide a viable strategy for enhancing tumor treatment.