Methylene blue associated with maghemite nanoparticles has antitumor activity in breast and ovarian carcinoma cell lines

Abstract

Background: Cancer constitutes group of diseases responsible for the second largest cause of global death, and it is currently considered one of the main public health concerns nowadays. Early diagnosis associated with the best choice of therapeutic strategy, is essential to achieve success in cancer treatment. In women, breast cancer is the second most common type, whereas ovarian cancer has the highest lethality when compared to other neoplasms of the female genital system. The present work, therefore, proposes the association of methylene blue with citrate-coated maghemite nanoparticles (MAGCIT–MB) as a nanocomplex for the treatment of breast and ovarian cancer. Results: In vitro studies showed that T-47D and A2780 cancer cell lines underwent a significant reduction in cell viability after treatment with MAGCIT–MB, an event not observed in non-tumor (HNTMC and HUVEC) cells and MDA-MB-231, a triple-negative breast cancer cell line. Flow cytometry experiments suggest that the main mechanism of endocytosis involved in the interiorization of MAGCIT–MB is the clathrin pathway, whereas both late apoptosis and necrosis are the main types of cell death caused by the nanocomplex. Scanning electron microscopy and light microscopy reveal significant changes in the cell morphology. Quantification of reactive oxygen species confirmed the MAGCIT–MB cytotoxic mechanism and its importance for the treatment of tumor cells. The lower cytotoxicity of individual solution of maghemite nanoparticles with citrate (MAGCIT) and free methylene blue (MB) shows that their association in the nanocomplex is responsible for its enhanced therapeutic potential in the treatment of breast and ovarian cancer in vitro. Conclusions: Treatment with MAGCIT–MB induces the death of cancer cells but not normal cells. These results highlight the importance of the maghemite core for drug delivery and for increasing methylene blue activity, aiming at the treatment of breast and ovarian cancer. Graphic Abstract: [Figure not available: see fulltext.]