Application Of Ultra-thin Two-dimensional MXene Materials Loaded With Barium Tungstate In Tumor Photothermal Therapy Under MRI/CT Dual-mode Imaging Navigation

As a typical carbon based two-dimensional material,MXene has been widely studied in recent years because of its unique properties.As one of the most early synthesized MXene materials,Ti₃C₂ has shown great potential in electrochemistry,sensing,nanomedicine and other fields.Due to the strong absorption in near infrared region-I?NIR-I?and high photothermal conversion efficiency,Ti₃C₂ nanosheets exhibit rapid heating characteristics under the irradiation of 808 nm laser,and show the potential to serve as tumor photothermal therapy reagents.Polyoxometalates?POMs?,a ultrasmall inorganic nanocluster with stable structure and physicochemical properties,has been widely applied in many fields including biomedical imaging,radiotherapy,photothermal therapy and catalysis.GdW₁₀-based POMs could be utilized as dual-mode contrast agents for magnetic resonance imaging?MRI?and X-ray computed tomography?CT?because of the Gd and W components,in order to accurately guide and monitor the process of tumor therapy.In this paper,we have synthesized a new type of composite nanosheets for dual-mode imaging guided efficient photothermal theranostics by covalent bonding GdW₁₀-based POM onto Ti₃C₂ nanosheets.The as-prepared composite nanosheets showed low cytotoxicity,and could be utilized for photothermal treatment under the irradiation of near infrared laser to kill tumor cells efficiently.In addition,due to the outstanding performance of POMs in MRI/CT dual-mode imaging,POMs-modified MXene nanosheets can accurately guide and monitor the whole process of photothermal therapy via MRI/CT dual-mode imaging,improve the efficiency of photothermal therapy,and ensure the safety of photothermal therapy.As for in vivo therapy,tumors of the mice in photothermal therapy treated group were completely eliminated within a short period after the treatment,and no recurrence occurred during the whole observation period.To sum up,the composite nanosheets show great potential in the theranostics of tumor.The full dissertation is divided into the following three chapters.In the first chapter,we mainly summarize the research progress of two-dimensional materials in the field of tumor thernostics,and the classification and progress of the theranostic functionalization of nanomaterials.In the second chapter,the synthesis and characterization of GdW₁₀@Ti₃C₂composite nanosheets were illustrated in detail,and its cytotoxicity,in vitro and in vivo curative effect were studied thoroughly.The GdW₁₀@Ti₃C₂ composite nanosheets have relatively uniform hydrodynamic diameter and high structural stability,and can be stably dispersed in various solutions.UV-vis-NIR spectrum indicated that the strong absorption in near infrared region is concentration dependent,and the GdW₁₀@Ti₃C₂ composite nanosheets could be heated-up rapidly under the irradiation of near infrared laser,ensuring it to be utilized as photothermal reagents for tumor therapy.In vitro cytotoxicity analysis showed that GdW₁₀@Ti₃C₂ composite nanosheets had low cytotoxicity and could kill cancer cells efficiently under near infrared laser irradiation.Through the confocal phagocytosis analysis,we observed that a large amount of GdW₁₀@Ti₃C₂ composite nanosheets were phagocytose by cancer cells after 4 h incubation,indicating their satisfying passive targeting effect.In vivo and in vitro MRI/CT imaging assays indicated that GdW₁₀@Ti₃C₂ composite nanosheets have better MRI and CT imaging performance,their longitudinal relaxation rate r₁=7.09 mM^-1 s^-1,CT imaging coefficient=20.33 HU/m M,and the signal intensities of tumor sections exhibited obvious alternation after the injection of composite nanosheets,hence GdW₁₀@Ti₃C₂ composite nanosheets would be ideal MRI/CT dual-mode imaging diagnostic reagents.Ultimately,in vivo experiments confirmed that dual-mode imaging guided and monitored precise and efficient photothermal therapy of GdW₁₀@Ti₃C₂ composite nanosheets in the tumor bearing mice also had a good effect,indicating that GdW₁₀@Ti₃C₂ composite nanosheets would be ideal efficient photothermal theranostic reagents for tumor therapy.In the third chapter,we summarize the experimental data and discuss the results,and then make an outlook about the application of GdW₁₀@Ti₃C₂ composite nanosheets in the efficient theranostics of tumor.