Intratumoral 198Au Nanobrachytherapy Reduces Tumor Growth and Metastasis in a Murine Model of Triple-Negative Breast Cancer

Abstract

Nanobrachytherapy (NB) uses radioactive nanoparticles (NPs) to deliver localized ionizing radiation within tumors, whereas photobiomodulation therapy (PBM) employs low-intensity light to modulate cellular responses. Here, we evaluated NB alone and combined with PBM using 198AuNPs and red laser irradiation in a murine triple-negative breast cancer (TNBC) model. Female mice were inoculated with 4T1 cells in the lower left mammary fat pad and, once tumors reached ∼0.1 cm3, were assigned to three groups: NB (intratumoral injection of ∼200 μCi 198AuNPs), PBM+NB (single red laser session before NB), and Control (PBS). Tumor progression, clinical signs, spleen mass, and lung metastases were evaluated over 23 days. Galectin-3 (Gal-3) expression was quantified by RT-qPCR, and biodistribution and dose delivery of 198AuNPs were assessed by gamma counting and Monte Carlo simulations. NB significantly reduced tumor growth, lung metastases, and splenomegaly and improved clinical status compared with controls, accompanied by decreased Gal-3 expression. Similar outcomes were observed with PBM+NB, with no additional therapeutic benefit compared with NB alone. Biodistribution confirmed preferential tumor retention of 198AuNPs, which declined over time. The estimated tumor dose rate was ∼9.34 mGy/s, decreasing to ∼4.14 mGy/s after 20 min, consistent with NP diffusion. Environmental dose estimates in the isolator remained below 34% of the tumor dose, supporting procedural safety with appropriate radiological protection. These findings demonstrate that 198Au-based NB effectively reduces tumor progression and metastatic burden in TNBC. Under the conditions tested, PBM did not modify therapeutic outcomes. The results support further investigation of localized radionuclide delivery using metallic NPs as an intratumoral radiation strategy.