Gold Nano-Rod (AuNR)-mediated plasmonic photothermal therapy in feline mammary carcinoma: assessing metastatic and nonmetastatic outcomes
摘要
Felines with mammary carcinoma (MC) often show aggressive metastatic behavior, largely driven by mammary cancer stem cells (MCSCs), which promote invasiveness and are resistant to standard therapies. However, these cells can be selectively eradicated using gold nanorod (AuNR)-mediated plasmonic photothermal therapy (PPTT). This study evaluated, for the first time, the potential influence of AuNRs-PPTT on the progression of MC by monitoring circulating MCSCs in the blood of cats with spontaneous forms of MC, both metastatic and non-metastatic, utilizing flow cytometry analysis (FCA).
MethodsThe study included ten adult, unspayed female cats diagnosed with mammary carcinoma. Of these, four exhibited metastases—three at the time of enrollment and one during the study. Participants were divided into two treatment groups based on tumor size: Group A (GA, n = 7) received PPTT alone, while Group B (GB, n = 3) underwent partial mastectomy of the affected gland followed by PPTT to the tumor bed. Circulating MCSCs were identified as CD133+ or CD44+/CD24− using FCA of 1 ml whole blood collected at two-week intervals for one year. MCSC counts were compared before and after the treatment, and their correlation with metastatic progression was evaluated.
ResultsAt the one-year follow-up, a 60% survival rate was documented, along with a statistically significant decrease (P = 0.00512) in circulating MCSC counts- compared to baseline- among nonmetastatic cats in both treatment groups. In the GA group, four nonmetastatic cats achieved complete tumor remission 6 to 8 weeks after treatment, with a median overall survival (OS) of 17.5 months. In the GB group, two patients without metastasis had a median OS of 12.5 months, with complete wound healing and no evidence of local recurrence or distant metastasis during the observation period. Conversely, lung metastasis continued to persist in the metastatic cats across both groups, accompanied by a statistically significant increase in circulating MCSC counts (P = 0.008).
ConclusionsThese findings suggest that MCSCs are significantly affected by AuNR PPTT in nonmetastatic cats; however, modifications in the treatment protocols are necessary for metastatic cats. Additionally, the FCA of circulating MCSCs serves as an accurate and noninvasive method for monitoring therapy in feline mammary cancer patients.