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

Investigating the anticancer efficacy of biogenic synthesized MgONPs: An in vitro analysis

“…Various nanoparticles have been reported to induce ROS formation, eventually stimulating various anticancer events, such as oxidative stress, lipid peroxidation, DNA damage, and destabilization of mitochondria, resulting in cell death by apoptosis and necrosis ( Alharthy et al, 2022 ; Tabrez et al, 2022b ; Zughaibi et al, 2022 ). A low level of ROS has been suggested to regulate cancer cell tumorigeneses, whereas a high-level causes severe cellular damage ( Youhannayee et al, 2019 ; Silva et al, 2021 ). Some studies also indicated that treating cells with various stress factors, such as anticancer drugs, increases ROS levels and induces cellular apoptosis by triggering proapoptotic signaling molecules ( Lampiasi et al, 2009 ; Azizi et al, 2017 ).…”

Chikungunya virus produced by a persistently infected mosquito cell line comprises a shorter genome and is non-infectious to mammalian cells

“…To confirm that CHIKV AA and MAYV AA lost their ability to infect mammalian cells, including humans, these viruses and parental CHIKV and MAYV were inoculated on primary cultured human fibroblasts isolated from dental pulp [25]. Before that, to increase the inoculum pressure over fibroblasts, CHIKV AA /MAYV AA were grown in Aag-2 cells in T-75 flasks as described in the Methods section.…”

“…Vero cells were grown in Dulbecco's Modified Eagle Medium (DMEM) high glucose (Sigma-Aldrich) supplemented with 10% FBS and 1× P/S solution at 37 °C under 5% CO 2 . Human fibroblasts isolated from dental pulp were kindly supplied by Dr Sonia N. Bao and details can be seen elsewhere [25]. These cells were grown under the same conditions as Vero cells.…”

Metal-Organic Framework-Based Nanotherapeutics With Tumor Hypoxia-Relieving Ability for Synergistic Sonodynamic/Chemo-therapy

“…In order to measure the production of ROS, 4T1 cells were cultured in vitro and incubated with DZCP + (DZCP combined with ultrasonic treatment) under hypoxia (1% oxygen) conditions for 3 and 6 h, respectively. The ROS/hypoxia detection kit was used (Figure 3B), the characteristics of which are the same as the reported method (Silva et al, 2021;Zhang et al, 2021). The generated ROS was detected in DZCP + -treated cells with the appearance of green fluorescence, demonstrating that ROS generation and tumor cells decrease under hypoxic conditions.…”