Application of manganese oxide nanocomposite coated with itaconic acid labeled with methotrexate in magnetic resonance imaging and radiotherapy

Abstract

In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) coated with biocompatible poly (dimethylaminoethyl methacrylate -Co- itaconic acid) polymers and targeted with methotrexate (MTX) to produce an efficient pH-sensitive targeted theranostic system. MnO2@Poly(DMAEMA-Co-IA) as a novel magnetic resonance imaging (MRI) contrast agent and radiosensitizing agent to improve RT efficacy during cancer treatment. While the MnO2 core NPs is dissociated into Mn+2 in this nanostructure, this increases T1 magnetic resonance signals in cancer cells in acid medium and acts as an established RT sensitizer that could cause endogenous H2O2 in the tumor microenvironment to decompose, producing oxygen and overcoming RT resistance attributed with hypoxia. The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and RT efficacy. Materials and methods: In this study, nanocomplexes based on manganese dioxide nanoparticles coated with itaconic acid polymer were synthesized and characterized. Methotrexate drug was loaded in these nanocarriers and the efficiency and drug loading capacity were calculated. Cytotoxicity studies for these drug nanocarriers were conducted on healthy (MCF 10A) and cancer (MCF 7) cell lines. Relaxation calculations were calculated and compared for nanocontrasts labeled with methotrexate as well as dotarm as a commercial contrast agent. Results: MnO2@Poly(DMAEMA-Co-IA) nanoparticles and nanoparticles loaded with MTX inhibited the viability of MCF 7 cells more effectively than free MTX after 24 and 48 hours, respectively, without Have significant toxicity. In addition, the negligible hemolytic activity of the final nanosystem showed good compatibility with blood. T1-weighted magnetic resonance imaging was performed to detect differential uptake of synthesized MnO2@Poly(DMAEMA-Co-IA)-MTX nanoparticles in malignant MCF 7 cells with high methotrexate receptor compared to normal MCF 10A cells with low methotrexate receptor. In magnetic resonance imaging, the produced theranostic nanoparticles showed an increase in contrast in response to acidic pH. As shown by in vitro assays, treatment of cells with MnO2@Poly(DMAEMA-Co-IA)-MTX before RT under hypoxic conditions significantly increased the therapeutic efficiency.