Experimental Study On Multi-modality Targeted Nanoprobe Diagnosis By MR Imaging And Bio-optical Imaging In Hepatocarcinoma

ObjectiveThrough the synthesis the R-GdMFs targeted probe,tumor targeted diagnisis was detected by Magnetic Resonance Imaging and Near infrared（NIR）fluorescence imaging in hepatocarcinoma.MethodsGadolinium（Gd）,ferroferric oxide（Fe₃O₄）,DIB-PEG-COOH,RGERPPR and fluorescent dyes Cy5.5 were selected to synthesis R-GdMFs multi-modality targeted nanoprobe.Transmission electron microscopy（TEM）,high resolution transmission electron microscope（HRTEM）,selected area electron diffraction（SAED）,the inductively coupled plasma atomic emission spectroscopy（ICP-AES）and energy dispersive X-ray（EDX）were used to measured its size,composition and performance;A cell uptake analysis of R-GdMFs nanoparticles was obtained by confocal laser scanning microscopy（CLSM）and flow cytometry（FCM）.The cytotoxicity of the as-synthesized R-GdMFs nanoparticles in vitro was assessed by an MTT assay,an LDH leakage assay and an intracellular ROS concentration measurement of the HepG2 cells.The MRI study was performed on a 3.0T MR imaging system and the in vivo fluorescent images were taken using small animal imaging systems.The impact on organs of nanoprobe was detected by HE staining.ResultsCharacterization of the R-GdMFs nanoprobes:The R-GdMFs nanoparticles are well dispersed and spherical in shape with an average particle size of 15 nm,and the clear core-shell structure was presented,the hydrodynamic radius was approximately 25nm.The probe respectively dissolved in water and DMEM,there are no distinct differences in the size and fluorescence intensity of the R-GdMFs nanoparticles compared with that dispersed in water after 14-day storage.The HepG2 cells show good uptake with the nanoprobes functionalized by RGERPPR.As shown by FCM,which clearly demonstrated that more R-GdMFs are taken up into the cells with longer incubation times and magnetic targeting accumulation.The R-GdMFs nanorobes could enrich the tumor site during blood circulation over time,the imaging results revealed that the R-GdMFs nanoparticles have the unique ability to simultaneously show strong MR imaging and NIR imaging in vivo.The histological analysis exhibited that there were no significant histological injuries observed in the major organs of the nanoprobes-injected mice.ConclusionsThe obtained R-GdMFs nanoparticles with a rational design are water-dispersible,have long-term stability,have excellent targeting,have controllable magnetic delivery and excellent biocompatibility with no impact on the cell and major organ functions.The R-GdMFs nanoprobes could synergistically enhanced T₁ and T₂-weighted MR/NIR fluorescence multimodality imaging in liver cancer model.