Nanobrachytherapy associated with photobiomodulation in a mouse model of induced breast tumor

Abstract

Breast cancers are responsible for a significant number of deaths among women, underscoring the urgent need for innovative therapeutic approaches to improve quality of life and increase survival rates. In this context, nanobrachytherapy (NB) and photobiomodulation therapy (PBM) have emerged as less invasive and promising alternatives. NB employs radioactive nanoparticles to optimize and target ionizing radiation, offering advantages such as reduced costs, toxicity, and side effects. PBM, which uses red or near-infrared radiation, has been investigated for its potential to radiosensitize tumor cells and/or radioprotect normal cells during cancer treatments. This study aimed to evaluate the impact of PBM combined with NB, enabled using radioactive gold nanoparticles (198AuNPs), for the treatment of triple-negative breast cancer (TNBC) in a murine model. Murine 4T1 cells were injected into the lower left mammary fat pad of female mice. When tumors reached approximately 0.1 cm3, the animals were randomly divided into three experimental groups: i) NB Group: animals received intratumorally injections of 198AuNPs (∼ 200 μCi); ii) PBM+NB Group: tumors were irradiated with a red laser (660 nm, 40 mW, 150 s, 6 J) in a single session before the injection of 198AuNPs; and iii) Control Group: animals were inoculated with PBS (phosphate buffered saline) but did not receive any treatment, although they were subjected to the same handling conditions. The mice were monitored for 23 days to assess tumor development, survival rates, clinical parameters, and the presence of lung metastases. Additionally, galectin-3 (Gal-3) protein levels were quantified via RT-PCR following euthanasia. The biodistribution of radioactive and non- radioactive AuNPs was analyzed through gamma photon counting and energy-dispersive X-ray spectroscopy (EDS), respectively. Monte Carlo (MC) simulations were performed to estimate the relative dose. The results showed significant tumor growth inhibition, improved clinical parameters, increased survival rates, and fewer lung metastases in the NB and PBM+NB groups compared to the Control group. Furthermore, Gal-3 levels were significantly lower in the treated groups. However, no statistically significant differences were observed between the NB and PBM+NB groups. Biodistribution analysis revealed greater accumulation of AuNPs in the tumor region, which decreased over time. MC simulations indicated a higher dose delivered to the tumor region. These findings suggest that NB is a promising approach for the treatment of TNBC. However, under the studied conditions, PBM therapy did not demonstrate synergy with NB.