Cytotoxicity and Antitumor Activity of Biogenic Silver Nanoparticles Against Non-Muscle Invasive Bladder Cancer

Abstract

Bladder cancer is the fifth most common form of malignancy in the United States, and for most of the last three decades, the treatment and outcomes for patients with this disease have not changed. Nanomedicine aims to provide the means to target chemotherapies directly and selectively to cancerous cells and enhance their therapeutic efficacy. In this scenario, we employed biogenic Silver Nanoparticles (AgNPs) as an anticancer agent against non-muscle invasive bladder cancer (NMIBC). Bladder cancer was chemically induced with N-methyl-N-nitrosourea (MNU) on C57BL/6Junib female mice and treated by intravesical route with biogenic silver nanoparticles concentrations of 0.5, 0.2, and 0.05 mg/mL. The histopathological analyzes showed the treated with AgNP 0.5 group presented 42.85% of pTa, 28.57% of pTis and 28.57% of pT1, indicating that this treatment was not effective in regressing the neoplastic lesions. MNU + AgNP 0.2 group showed 28.57% of tumor regression, being these animals showed flat hyperplasia (28.57%). Finally, treatment with 0.05 AgNP led to 57.13% of tumor regression, with 14.28% of the animals showing normal urothelium and 42.85% showing flat hyperplasia, considering a benign lesion. Further, to understand the antitumor effect of AgNPs, we evaluated the molecular mechanism of cytotoxicity in human bladder carcinoma 5637 cell. The results showed the dose-time dependent cytotoxicity, and detailed analysis demonstrated the induction of cell death via apoptosis. Besides, we found that AgNP inhibition in cell migration and proliferation. Thus, these findings confirm the antitumor properties of AgNPs and suggest that they may be a cost-effective alternative and promising candidate for the treatment of bladder cancer.