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

Abstract

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 (r 1 = 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.

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics

“…Gadolinium is a common commercial MRI contrast agent with relatively good reflexivity and low biotoxicity. It has been widely used in the field of biomedicine for cancer theranostics [ 114 – 116 ]. However, owing to its own shortcomings, its application can occasionally cause patient to develop nephrogenic systemic fibrosis.…”

Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer

“…There are two strategies used to improve the therapeutic efficiency of radiotherapy. The first one used materials containing high Z elements, such as gold nanoparticles, bismuth-based nanoparticles, hafnium-based nanoparticles, gadolinium-based nanoparticles, and platinum nanoparticles to enhance X-ray absorption, generate electrons and induce a large amount of free radicals (Liu et al., 2017 ; Yu et al., 2017 ; Li et al., 2019 ; Kuang et al., 2020 ; Wu et al., 2021 ). However, the clinical translation of inorganic materials is limited by their high cost and safety issues.…”

Biomedical Applications of Lanthanide Nanomaterials, for Imaging, Sensing and Therapy

“…Ye Kuang and colleagues doped Gd into HfO2 to create a Gd 2 Hf 2 O 7 nanoparticle that utilizes the Gd as an MRI contrast agent and Hf as a radiosensitizer. They surface modified the nanoparticle with RGD peptides and loaded the particle with cisplatin to a create a potential MRI-guided combined chemo-/ photothermal-/radiotherapy nanoplatform for drug-resistant tumors [45]. McLeod et al incorporated a Gd(III) complex into a Zr-based MOF (Metal-organic framework) through solvent-assisted ligand incorporation (SALI) and tested the combined MOFs as a potential MRI contrast agent [46].…”