Impacts of methotrexate graphene oxide modified magnetic nanoparticles combined with pH regulating agents on breast cancer

Abstract

Background: The current breast cancer treatment modalities in clinical need to be improved to tackle with pitfalls such as undesired side effects and drug resistance which cause disease relapse after a vigorous treatment. Due to unique physicochemical features of graphene-based nanosystems, they offer opportunity in this regard.

Purpose: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Materials & Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic and targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (11) laser irradiation.The NPs were characterized using FTIR, TEM, DLS, VSM, and XRD analysis, and their biological and photothermal effects were evaluated using FITC-labeled annexin V and MTT assay in MDA-MB231 and MCF-7 breast cancer cells. To determine the efficacy of GO-MNPs for PTT, low doses of the near-infrared laser irradiation were used. Results: The NPs exhibited layered and monodispersed morphology with an average size of 176.1 nm. The FT-IR analysis confirmed the surface modification of the NPs. The flow cytometry analysis revealed that MTX conjugated PEGylated NPs could significantly internalize by the folate receptors (FRs)-positive MDA-MB231 and MCF-7 cells and result in profound toxicity as compared to single PTT or chemotherapy. Conclusion: Our findings suggest that the GO-SPION- MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostics against breast cancer.