3210 - Synergistic Physicochemical Radiosensitization of HfO 2 Nanoparticles: Integrating Monte Carlo Simulation with Experimental Validation
Presenter(s)
Z. Zhao1,2, H. Wang3,4, Y. Pan4, and C. Zhang4; 1Peking University, Beijing, China, 2Peking University Third Hospital, beijing, China, 3Cancer Center,Peking University Third Hospital, Beijing, China, 4Peking University Third Hospital, Beijing, China
Purpose/Objective(s): This study aims to delineate the complete radiosensitization chain of hafnium dioxide (HfO2) nanoparticles by quantitatively integrating physical dose enhancement and chemical radical amplification mechanisms. We hypothesized that HfO2 nanoparticles maximize sensitization under low-energy X-ray irradiation through synergistic physical and chemical pathways, and that subcellular targeting strategies significantly modulate this efficacy.
Materials/Methods: Monte Carlo (MC) simulations were performed using TOPAS and TOPAS-nBio toolkits. A realistic spherical cell model was constructed with specific elemental compositions for the cytoplasm, nucleus, and mitochondria. Physical Dose Enhancement Factors (DEF) and chemical G-values for hydroxyl radicals (·OH), hydrated electrons (e-aq), and hydrogen peroxide (H2O2) were quantified for various nanoparticle sizes (2.5–500 nm) and incident X-ray energies (50 keV–6 MeV). Subcellular localization scenarios, including nuclear, cytoplasmic, and mitochondrial targeting, were evaluated. Experimentally, 5nm HfO2 nanoparticles were synthesized and characterized via TEM and XRD, with radiosensitization efficacy validated in 4T1 cells under 160 kVp X-ray irradiation.
Results: MC simulations indicate that the DEF is highly energy-dependent, peaking at ~8–9 under 100 keV irradiation, while remaining negligible (~1.0) at 6 MeV. Short-range DEF within 20 nm of the nanoparticle surface reached magnitudes of 103. Nuclear targeting yielded the highest global radiosensitization (DEF > 2.02) compared to cytoplasmic and mitochondrial targeting. Radiochemical modeling revealed a 1.6-fold increase in ·OH yield under 100 keV irradiation. Notably, HfO2 suppressed H2O2 formation (G-ratio ~0.85) due to high-density radical recombination at the nanoparticle interface. Ultra-small nanoparticles (2.5–5 nm) exhibited significantly superior radical generation per unit mass compared to 500 nm particles. Experimental results confirmed successful synthesis of high-purity monoclinic HfO2 (~5 nm) and demonstrated a concentration-dependent decline in cell viability to 46% at 100 µg/mL under irradiation.
Conclusion: This work establishes that HfO2 nano-radiosensitization is optimized in the keV energy range through localized physical energy deposition and enhanced ·OH production. Strategic nuclear localization is critical for maximizing biological damage. These findings provide a theoretical and parametric foundation for the rational design of high-efficiency targeted nano-radiosensitizers in precision radiotherapy.