Proton beam-induced effects of platinum nanoparticles and their intracellular localization.

This study investigates the effects of platinum nanoparticles (Pt NPs) on breast cancer cell lines (MCF7 and MDA-MB-231) under proton beam irradiation, with a focus on nanoparticle accumulation behavior, cytotoxicity and radiosensitization. Platinum NPs used in this research exhibited a uniform, flower-like morphology with an average size of 26.2 ± 3.9 nm and showed no agglomeration. Cytotoxicity assays revealed that Pt NPs induced time- and concentration-dependent decrease in cell viability, with significant toxic effects observed at concentrations ≥ 0.375 mM. Moreover, holotomographic imaging demonstrated dynamic nanoparticle accumulation in both cell lines, initially localizing at the membrane and progressively internalizing over time. Importantly, no specific accumulation site preference was detected. Quantitative analysis showed that Pt NP uptake by MCF7 cells was approximately twice that of MDA-MB-231 cells, with simulation models aligning closely with experimental data (86 % and 90 % fit, respectively). Proton irradiation studies indicated a marked radiosensitizing effect of Pt NPs, with cell viability reduced by up to 85 % at higher NP concentrations and radiation doses (10 Gy). These findings underscore the potential of flower-like Pt NPs as effective radiosensitizers in proton therapy, owing to their high cellular uptake, surface reactivity and cytotoxicity.