Application Of Functionalized Cu 3 BiS 3 Nanomaterials In Dual Mode Imaging And Phototherm/Photodynamic Therapy

Ternary metal sulfide?Cu₃BiS₃?is a kind of metal-sulfide materials which has been proved to be a new type of photothermal therapeutic agent.Due to its strong absorption in the NIR,under the NIR laser irradiation,the temperature of the Cu₃BiS₃ nanoparticle aqueous solution increased rapidly.Chlorin e6?Ce6?is a commonly used photosensitizer.Irradiated with a specific wavelength of light can activate the photosensitizer,and the stimulated photosensitizer then transfers its energy to the surrounding oxygen molecules,resulting in the formation of cytotoxic reactive oxygen species?ROS?that can cause tumor cell ablation.In this thesis,we have prepared a novel multifunctional nanocomposite material,in which Cu₃BiS₃ nanoparticles were modified with photosensitizer Ce6,a fluorescent molecule that in the meantime could form chelate complex with Gd³⁺,and finally covalently bound with a targeted ligand folic acid?FA?.The obtained nanocomposites exhibit low cytotoxicity,and are able to trigger both photothermal therapy?PTT?and photodynamic therapy?PDT?.Therefore,this combination of photothermal and photodynamic therapy can effectively resist tumors in vivo and in vitro.In vivo combined PTT and PDT treatment is then carried out after systemic administration of the composites,achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone.In addition,this material can also be used as magnetic resonance imaging?MRI?and X-ray computed tomography?CT?dual-mode contrast agents.Hence,this multifunctional materials show promising application potential in the imaging and synergistic treatment of cancer.The full text is divided into four chapters.In the first chapter,we summarize the types and research progress of photothermal agents and photosensitizers in recent decades,as well as the types of MRI and CT contrast agents and their research trend.In the second chapter,the Cu₃BiS₃-PEG-(Ce6-Gd³⁺)-FA multifunctional nanocomposites were prepared and characterized.We also investigated the photothermal / photodynamic and MRI / CT imaging properties of the nanocomposites.The synthesized Cu₃BiS₃-PEG-(Ce6-Gd³⁺)-FA materials are in good morphology and small size,and can be dispersed in the physiological solutions.The experiments based on the solution of Cu₃BiS₃-PEG-(Ce6-Gd³⁺)-FA demonstrated that this material has a strong absorption in the NIR region,and it not only can be used asphotothermal agent,but also can be used as photodynamic therapy agent due to the modified photosensitizer Ce6.The relaxation of material is,r1 = 6.8 mM-1S-1,r2 = 12.0mM-1S-1?r2/r1 = 1.75?,indicating that this material is suitable as a T1 imaging contrast agent.Compared the CT imaging of the material with Iohexol,this material showed better CT imaging effect than iodohydrin.Therefore,Cu₃BiS₃-PEG-(Ce6-Gd³⁺)-FA has both tumor imaging and combination synergistic effects.The third chapter is to explore the cytotoxicity of materials,in vivo MR / CT imaging,and in vitro and in vivo photothermal/photodynamic therapy.In vitro cell experiments have shown that this material has low cytotoxicity in folate recepter high expression and low expression cells.The laser confocal microscopy experiment confirmed that the material could target HeLa cells highly expressing folate receptor.At the same time,the in vivo MR and CT imaging results indicate that the material can be used as a dual-mode imaging contrast agent.Finally,we found that the material in the tumor-bearing mice also showed good photothermal / photodynamic synergistic effects.So this material has photothemal / photodynamic synergistic effects under the guidance of MR and CT dual-mode imaging.In the fourth chapter,we summarize the experimental data and results,and then make an outlook about the diagnosis and treatment of nano materials in the future.