Application Of Magnetic Resonance Nanoparticles In HER-2 Positive Breast Cancer

Part ? Application of multimodal imaging and photothermal therapy in HER-2 positive breast cancer[Objective]To create multifunctional super paramagnetic iron oxide nanoparticles(SPIONs)based on anti-HER2 monoclonal antibody—trastuzumab and indocyanine green(ICG).To test whether the nanoparticles(NPs)could target HER-2 receptors on breast cancer cells in vitro and vivo.[Materials and Methods]Fe3O4-trastuzumab-ICG NPs was created.A series of characterization of the NPs were tested.The targeted cell uptake of Fe3O4-trastuzumab-ICG in vitro was identified by TEM.In vivo,MR imaging was conducted on mice engrafted with HER-2 overexpressed SK-BR-3 cells.After injection of NPs into the tail vein of breast cancer animal models,we observed whether NPs could aggregate in the tumor site by MRI and fluorescent imaging.When the NPs was gathered at the tumor site,the near infrared thermal imaging system was used to monitor the temperature of tumor in the near infrared radiation.[Results]The Fe3O4-trastuzumab-ICG NPs was successfully constructed.The size of NPs was 25.93 nm.The absorption peak of NPs was 828 nm,which was the same as the emission wavelength of ICG.NPs had a high relaxation rate(r2),about 107.65 s-1/mMFe.The maximum temperature of NPs solution could reach 57.8? after continuous near infrared laser irradiation.The TEM imaging showed that the NPs could target SK-BR-3 cells and enter the endoplasmic reticulum.MRI showed the lowest T2 relaxation time in the tumor site at 24 h following the NPs injection.Animals in theFe3O4-trastuzumab-ICG group tended to have higher ?T2,and these differences were statistically significant(P<0.05)compared to animals in three control groups.The fluorescence imaging showed that Initially,NPs was concentrated in the intraperitoneal organs and tumor site,then excreted through the bladder.After 24 hr,there was an obvious aggregation in the tumor site.The near infrared thermal imaging experiments showed that the temperature of tumor could reach more than 43? needed to kill the tumor cells,after the laser irradiation.[Conclusions]This study revealed that Fe3O4-trastuzumab-ICG NPs had the potential to become a theranostic agent for HER-2 positive breast cancer.Part ? Application of magnetic resonance nanoparticles in evaluating the expression of HER-2 in breast cancer animal models[Objective]To create super paramagnetic iron oxide nanoparticles(SPIONs)based on trastuzumab.To test whether the nanoparticles(NPs)could target human epidermal growth factor receptor-2(HER-2)receptors on breast cancer cells in vitro and vivo.And to explore the non-invasive method of evaluating HER-2 expression in breast cancer models by magnetic resonance imaging(MRI).[Materials and Methods]Fe3O4-trastuzumab NPs were created.A series of characterization of the NPs were tested.HER-2 expression of SK-BR-3,MDA-MB-453 and MDA-MB-231 breast cancer cells was verified.The uptake ability of three breast cancer cells to NPs was observed by transmission electron microscopy.The mice engrafted with three breast cancer cells was established.After injection of NPs into the tail vein of mice,we observed correlation between ?T2 of tumor site and HER-2 expression.[Results]Fe3O4-trastuzumab NPs were successfully constructed.The hydrodynamic dimension peak of NPs was 24.12 nm.NPs had a high relaxation rate,about 107.65 mM-1s-1.The transmission electron microscopy imaging showed that the NPs could target SK-BR-3 and MDA-MB-453 cells and enter the endoplasmic reticulums.MRI showed the ?T2 of the tumor site at 24 h following the NPs injection was linearly correlated with the degree of HER-2 expression.[Conclusions]Fe3O4-trastuzumab NPs had the potential to become a tool for evaluating the HER-2 expression of breast cancer.