Theranostic Nanoparticles With Aggregation-induced Emission And MRI Contrast Enhance Characteristic Hepatocellular Carcinoma Dual-modal Imaging

Objective SPIO/AIE@HA-g-PZLL nano-probe was prepared to study its physical and chemical properties,biological safety,MRI/fluorescence dual-mode imaging ability and photodynamic therapy effect.Methods 1.Amphiphilic polymer HA-g-PZLL was prepared by click chemical reaction and self-assembled into SPIO/AIE@HA-g-PZLL nano-probe together with aggregation-induced Luminescence?AIE?and superparamagnetic iron oxide?SPIO?.Experiments with Fourier's Infrared spectrometry,ultraviolet absorption spectroscopy and nuclear magnetic resonance were conducted to confirm the completion of the chemical reaction and the production of the target substance.The dynamic light scattering?DLS?and transmission electron microscopy?TEM?showed that the SPIO/AIE@HA-g-PZLL nanoparticles were uniform in size.The in vitro imaging ability of SPIO/AIE@HA-g-PZLL and the ability of SPIO/AIE@HA-g-PZLL to produce singlet oxygen under white light irradiation were measured by single-line oxygen detector?ABDA?.2.The Fluorescence microscope/Confocal Fluorescence microscopy and Flow cytometry were used to measure the fluorescence imaging ability of the prepared materials,as well as the generation of reactive oxygen species?ROS?and tumor killing effects under white light irradiation.The in vitro uptake of SPIO/AIE@HA-g-PZLL,biological safety and fluorescence imaging properties of nanoparticles were studied by Prussian blue staining,Reactive Oxygen Species Assay Kit?DCFH-DA?and MTT test,to study the ROS production and cytotoxic effect to Hep G2 cells when exposed to white light.3.In order to explore the fluorescence imaging ability and T₂ signal contrast enhancement of SPIO/AIE@HA-g-PZLL in vivo,experiments of fluorescence imaging and magnetic resonance imaging?MRI?were performed on subcutaneous Hep G2 tumor-bearing mice using a small animal imaging system and 3.0 T MRI.Results 1.We successfully prepared SPIO/AIE@HA-g-PZLL nanoparticles with an average diameter of about 184 nm.It has good ability of near-infrared fluorescence emission and T2relaxation.The prepared nanoparticles have good fluorescence stability.And under white light irradiation,these nanoparticles can produce singlet oxygen.2.We demonstrated that the synthesized SPIO/AIE@HA-g-PZLL can target CD44overexpressed cancer cells in vitro and in vivo,which can be ingested by Hep G2 cells and produce enough ROS to kill tumor cells under white light irradiation,it is prospective to be used in tumor photodynamic therapy guided by MRI/FL dual-mode imaging.Conclusion We successfully prepared the MRI/fluorescence dual-mode agent SPIO/AIE@HA-g-PZLL,which can target tumor cells actively and significantly inhibit the growth of tumor cells through photodynamic therapy.