Preparation of MnO 2 @poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application

A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX). The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy. The targeted NPs MnO @Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T -weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO @Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO @Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy. We draw the conclusion that using MnO @Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells.