Ag-Bi2S3@BSA bimetallic nanoparticles for enhanced radiotherapy of breast cancer with integrated in vitro and Monte Carlo study

Bimetallic nanoparticles have emerged as promising radiosensitizers for improving the efficacy of cancer radiotherapy by enhancing local radiation energy deposition while maintaining acceptable biocompatibility. In this study, we developed and evaluated a novel Ag–Bi₂S₃@BSA bimetallic nanoplatform using an integrated experimental–computational approach combining in vitro biological evaluation with Monte Carlo (MCNPX) simulation. Ag–Bi₂S₃ nanoparticles were synthesized and coated with bovine serum albumin (BSA) to improve colloidal stability and biocompatibility. Their physicochemical properties were characterized using Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet–visible (UV–Vis) spectroscopy, and X-ray diffraction (XRD). Radiosensitizing efficacy was evaluated in 4T1 breast cancer cells using the MTT assay following irradiation with a 6 MV X-ray beam. In parallel, Monte Carlo simulations were performed to quantify the physical dose enhancement factor (DEF) at different nanoparticle concentrations. The Ag–Bi₂S₃@BSA nanoparticles enhanced radiation-induced cytotoxicity in a concentration-dependent manner, with the lowest cell viability (10.2%) observed at 600 µg/mL under 6 Gy irradiation. Consistently, the Monte Carlo simulations predicted the highest physical DEF at the same nanoparticle concentration. Although the simulated DEF represents physical dose enhancement rather than biological radiosensitization, the agreement between the computationally predicted optimal concentration and the experimental findings supports the value of integrating computational dosimetry with biological validation during nanoparticle optimization. These results identify Ag–Bi₂S₃@BSA as a promising bimetallic radiosensitizer for preclinical investigation and provide a rational framework for the future development and evaluation of multifunctional nanoparticle-assisted radiotherapy.