Dual-Stimuli-Responsive Multifunctional Gd₂Hf₂O₇ Nanoparticles for MRI-Guided Combined Chemo-/Photothermal-/Radiotherapy of Resistant Tumors

The design and synthesis of a novel generation of a nanoscaled platform with imaging-guided therapy remain a real challenge. It can not only improve the imaging sensitivity of tumor tissues for guiding all kinds of treatments but also reduce the harm for healthy tissues. Here, polydopamine (PDA), polyethylene glycol (PEG), and c(RGDyK) peptide (RGD)-modified and cisplatin-loaded Gd₂Hf₂O₇ nanoparticles (Gd₂Hf₂O₇@PDA@PEG-Pt-RGD NPs) are designed for magnetic resonance imaging (MRI)-guided combined chemo-/photothermal-/radiotherapy of resistant tumors. The as-prepared NPs display high relaxivity (r₁ = 38.28 mM^-1 s^-1) as an MRI contrast agent because of their ultrasmall size and surface modification with polyacrylic acid and PDA. Gd₂Hf₂O₇@PDA@PEG-Pt-RGD NPs exhibit pH and NIR dual-stimuli responsiveness for cisplatin release. Based on competent NIR absorption and high X-ray attenuation efficiency, Gd₂Hf₂O₇@PDA@PEG-Pt-RGD NPs show potential photothermal effect by exposing to an 808 nm NIR laser and significantly improve the generation of reactive oxygen species after X-ray radiation. Combined chemo-/photothermal-/radiotherapy can effectively treat the resistant A549R cells, providing the enhanced therapeutic efficiency to cancer tissues and the reduced side effect to healthy tissues. Furthermore, Gd₂Hf₂O₇@PDA@PEG-Pt-RGD NPs present no obvious toxicity during the treatment, which demonstrates the potential as an efficient MRI-guided combined chemo-/photothermal-/radiotherapy nanoplatform for drug-resistant tumors.