Engineering Hafnium Oxide-Based Nanoplatforms for Precision Radiosensitization.

Abstract

Hafnium oxide (HfO₂)-based nanomaterials are emerging as powerful tools to enhance radiotherapy by utilizing their high atomic number (Z). By depositing a greater radiation dose directly within tumors, they offer a promising route to improve treatment efficacy. This review traces the development of HfO₂ nanoradiosensitizers, starting with the clinically established NBTXR3, an approved hafnium-based benchmark for several solid tumors. We analyze the structural characteristics and radiosensitization mechanisms of nanoscale HfO₂, which include improved X-ray absorption, radical generation, and immunomodulation. Key synthesis methods such as sol-gel, precipitation, and hydrothermal approaches are evaluated in detail, with emphasis on their tunable parameters and reproducibility. Recent progress focuses on material optimization through size control, surface engineering, composite design, and Hf-MOFs, as well as combination strategies. Despite encouraging preclinical results, challenges remain in scalable fabrication, long-term biosafety, and clinical translation. Future directions point toward smart stimuli-responsive platforms and multimodal theranostic systems. This review highlights the potential of HfO₂ to precision radiotherapy while acknowledging existing translational challenges.