Preparation of MnO2@poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application.

OBJECTIVE: A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO2 NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX). MATERIALS AND METHODS: 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. RESULTS: The targeted NPs MnO2@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. T1-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO2@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 MnO2@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy. CONCLUSION: We draw the conclusion that using MnO2@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.

Predicting the Risk of Radiation Pneumonitis and Pulmonary Function Changes after Breast Cancer Radiotherapy.

BACKGROUND: Radiotherapy plays an important role in the treatment of breast cancer. In the process of radiotherapy, the underling lung tissue receives higher doses from treatment field, which led to incidence of radiation pneumonitis. OBJECTIVE: The present study aims to evaluate the predictive factors of radiation pneumonitis and related changes in pulmonary function after 3D-conformal radiotherapy of breast cancer. MATERIAL AND METHODS: In prospective basis study, thirty-two patients with breast cancer who received radiotherapy after surgery, were followed up to 6 months. Respiratory symptoms, lung radiologic changes and pulmonary function were evaluated. Radiation pneumonitis (RP) was graded according to common terminology criteria for adverse events (CTCAE) version 3.0. Dose-volume parameters, which included percentage of lung volume receiving dose of d Gy (V5-V50) and mean lung dose (MLD), were evaluated for RP prediction. Pulmonary function evaluated by spirometry test and changes of FEV1 and FVC parameters. RESULTS: Eight patients developed RP. Among the dose-volume parameters, V10 was associated to RP incidence. When V10<40% and V10≥40% the incidences of RP were 5.26% and 61.54%, respectively. The FEV1 and FVC had a reduction 3 and 6 months after radiotherapy, while only FEV1 showed significant reduction. The FEV1 had more reduction in the patients who developed RP than patients without RP (15.25±3.81 vs. 9.2±0.93). CONCLUSION: Pulmonary function parameters, especially FEV1, significantly decreased at 3 and 6 months after radiotherapy. Since most patients with breast cancer who developed RP did not show obvious clinical symptoms, so spirometry test is beneficial to identify patients with risk of radiation pneumonitis.

The effect of SiO2/Au core-shell nanoparticles on breast cancer cell's radiotherapy.

INTRODUCTION: Recently it has been shown that radiation dose enhancement could be achievable in radiotherapy using nanoparticles (NPs). In this study, evaluation was made to determine efficiency of gold-silica shell-core NP in megavoltage irradiation of MCF7 breath cancer cells. MATERIALS AND METHODS: Gold-silicon oxide shell-core NPs were obtained by conjugation of gold NP with amine or thiol functionalized silica NPs (AuN@SiO2 and AuS@SiO2). Cellular uptake and cytotoxicity of NPs were examined by fluorescent microscopy and MTT assay, respectively. MCF-7 breast cancer cells were treated with both NPs and irradiation was made with X-ray energies of 6 and 18 MV to the absorbed dose of 2, 4 and 8 Gy using Simense linear accelerator. The efficiency of radiation therapy was then evaluated by MTT and Brdu assay, DAPI staining and cell cycle analysis. RESULTS: TEM images indicated that synthesized NPs had average diameter of 25 nm. Cellular uptake demonstrated that the internalization of AuS@SiO2 and AuN@SiO2 NPs amounted to 18% and 34%, 3 h post treatment, respectively. Nontoxicity of prepared NPs on MCF-7 cells was proved by MTT and Brdu assays as well as DAPI staining and cell cycle studies. The highest enhancement in radiation dose was observed in the cells that irradiated with radiation energy of 18 MV and absorbed of 8 Gy at NPs concentration of 200 ppm. The Brdu findings revealed that the cytotoxicity and apoptosis on MCF-7 cells are dose dependent with a significantly more death in AuN@SiO2 (amine) exposed cells (p < .05). Analysis also revealed interruption in cell cycle by demonstrating lack of cells, in S phase in amine treated cells (AuN@SiO2) at given dose of 8 Gy using 18 MV X-ray in comparison to thiol treated cells. CONCLUSIONS: Based on the results of the study it can be concluded that the gold-silicon oxide shell-core NPs could play an effective role in radiotherapy of MCF-7 breast cancer cells.