Hafnia-basierte Nanopartikel zur Bildgebung und Therapie : Anpassung der physikalisch-chemischen Eigenschaften und Wechselwirkungen mit biologischen Entitäten : tailoring the physicochemical properties and itneractions with biological entities

Abstract

Cancer therapy remains a major global issue. While treatment modalities such as surgical resection, chemotherapy, radiotherapy, and thermal ablation have increased patient survival, resistance acquired in the course of the therapy eventually weaken the overall therapeutic success. In order to maximize treatment efficacy and minimize side effects, target cell selectivity is key. The therapy should be delivered exclusively to the tumor cells with minimal effects on healthy tissue. Various approaches have been developed to limit the radiation resistance while simultaneously enhancing the efficacy and safety of radiotherapy. Nanoparticles (NPs) hold promise as imaging probes and radiosensitizers in order to increase specificity. However, despite much excitement in the scientific community, translation of nanoparticle-based concepts has suffered from significant translational gaps, particularly in the field of biomedicine [23]. Among the nanomedicine-based products which have successfully been commercialized, the majority are based on liposomes. Other marketed nanomedicines include polymeric nanostructures and iron oxide nanoparticles [16, 30, 44]. Among the plethora of nanomaterials with feasible properties, hafnium dioxide has recently attracted attention due to the high dielectric constant ( = 25), high melting point (2758 °C), high atomic number (Z = 72), high density (9.7 g cm−3), high index of refraction, transparency to visible light (5.3–5.9 eV band gap), and chemical inertness. A HfO2 nanoparticle based formulation (NBTXR3, Nanobiotix) used as radiosensitizer has recently been submitted for market approval [44]. However, the understanding of the material properties, and especially its potential as a matrix for multimodal theranostic bioimaging combining x-ray imaging and radiosenzitation with lanthanide doped luminescence and MRI imaging, is vastly limited.