Dosimetry and chemical yield analysis of metal nanoparticles in FLASH radiotherapy: a Monte Carlo study

<i>Objective.</i>To investigate the influence of high-<i>Z</i>metallic nanoparticles (NPs) (Au, Ag, Pt) influence both physical dose deposition and radiochemical yields (⋅OHand H₂O₂) under conventional dose rate (CDR) and ultra-high dose rate (FLASH) irradiation, and to explore whether their presence modulates the FLASH effect, either enhancing or suppressing it depending on context.<i>Approach.</i>Monte Carlo simulations were performed using the TOol for PArticle Simulation-nBio/Geant4-DNA toolkit to model water radiolysis in the presence of a 50 nm metallic NP. Electron and photon beams of 1 MeV were delivered under multi-source configurations with varying inter-source distances, representing both CDR and FLASH-like conditions. The evolution of chemical species was tracked from 1 ps to 1 ms, and<i>G</i>-values for⋅OHand H₂O₂were extracted.<i>Main results.</i>NPs increased local energy deposition through the emission of low-energy secondary electrons; however, chemical yields exhibited nonlinear and configuration-dependent behavior. Under FLASH-like conditions, H₂O₂yields were consistently reduced, and this suppression was further modulated by NP type and source geometry. In some cases, NPs acted as radiosensitizers (increased⋅OHyields), while in others they showed radioprotective trends (reduced⋅OHand H₂O₂). These effects stem from competing mechanisms including radical-radical recombination, scavenging at NP surfaces, and spatial heterogeneity of secondary electron distributions (based on the inter-track and intra-track analysis).<i>Significance.</i>This work demonstrates that NP-assisted FLASH radiotherapy involves a complex interplay between physical and chemical processes, where increased dose deposition does not always translate into higher radiochemical yields. The dual role of NPs-as both potential radiosensitizers and radioprotectors-underscores the need for careful parameter optimization and experimental validation before clinical translation of NP-enhanced FLASH protocols.