The Construction And Anti-tumor Application Of Gold/Palladium And Gold/Platinum Nanocomposites

In recent years,cancer still seriously affects human life and health,longevity and quality of life after disease and recovery,and it is a major problem that needs to be solved by the development of modern life science and biomedical technology.Unlike normal tissues,the extremely complex microenvironment of tumor cells,such as uneven vascular distribution,lack of oxygen,acidic p H,redox imbalance and abnormal metabolism,which not only provides convenient conditions for tumor occurrence,unlimited proliferation and metastasis,but also provides specific targets for targeted delivery and activation response of nanoplatforms.At present,the traditional treatment methods used in clinic,such as surgery,chemotherapy and radiotherapy,are still systemic treatment strategies without tumor specific killing ability.It is urgent to develop new treatment strategies to improve tumor treatment efficiency and improve treatment effect.In recent years,with the rapid development of nanotechnology,nanocomposites with complex functions have been designed for highly specific tumor imaging and effective tumor therapy.This paper designs and constructs gold/palladium and gold/platinum nanocomposites by advanced nanotechnology,investigates the physicochemical properties of the bimetallic nanostructures,and explores their anti-tumor physiological activities in the body.And through the loading of chemotherapeutic drugs and the introduction of tumor multimodal imaging,realizes visual anti-tumor combined treatment methods,which provides novel design ideas and technical support for the application of nanomedicine in tumor treatment.The detail research works are as follows:1)In Chapter 2,based on the high-Z elements,optical properties,photothermal effect and inherent enzyme-like activity of noble metal nanomaterials,it’s hopeful to develop the applications of Au,Pd and Pt nanocomposites in the field of biomedical related disease diagnosis and treatment.In this chapter,we successfully synthesized dendritic Au@Pt bimetallic nanoparticles through one-step method,which exhibited uniform size,regular morphology and outstanding photothermal conversion efficiency.The optical properties of Au@Pt NPs could be easily manipulated by tailoring the surface plasmon resonance effect between the Au core and Pt shell,and the tunable absorption of Au@Pt NPs was obviously enhanced and red-shifting compared to Au NPs.In addition,we designed and synthesized a two-dimensional bimetallic core-shell nanostructure Pd@Au,Pd@Au was characterized with uniform size,clear hexagonal morphology,excellent optical properties,good photothermal efficiency,outstanding photostability and effective catalysis.Pd@Au could produce O₂continuously and persistently through circulating catalytic reaction.Thus,this efficient catalysis effect of Pd@Au is expected to overcome a series of detection and treatment problems caused by tumor hypoxia in clinical application applications.2)In Chapter 3,intend to solve the defects of photothermal therapy,such as lack of ideal photothermal agents or insufficient penetration depth of near-infrared laser,and enhance the therapeutic effect of photothermal therapy in practical clinical medical application.In this chapter,successfully synthesized dendritic Au@Pt and two-dimensional Pd@Au nanomaterials,such as near-infrared photothermal agents,were used in the application of anti-tumor photothermal therapy.Au@Pt and Pd@Au existed unique optical properties,outstanding photothermal conversion efficiency,excellent photothermal properties,good biocompatibility and negligible cytotoxicity,and were demonstrated for effective anti-tumor photothermal therapy in xenograft tumor mouse model.Overall,Au@Pt and Pd@Au have shown great potential as new photothermal agents,provide new ideas to investigate the fantastic physicochemical properties,catalysis abilities and physiological functions for the field of bionanomedicines.3)In Chapter 4,in order to solve the inherent defects of radiotherapy in actual clinical medical application,such as the toxic and side effects from X-ray radiation to adjacent normal soft tissue,and the insufficient local oxygen content of solid tumor tissue and so on,we used the successfully synthesized and characterized two-dimensional Pd@Au-PEG nanostructure,realized the combined anti-tumor photothermal and radiotherapy therapy to overcome hypoxia-induced radiotherapy resistance.Pd@Au-PEG was characterized with good biocompatibility,excellent catalytic stability to harsh condition and inherent catalase-like ability.Pd@Au-PEG could produce high contrast for multimodal tumor imaging like X-ray,photoacoustic and photothermal imaging.Meanwhile,Pd@Au-PEG were employed for catalysis of overexpressed endogenous H₂O₂in a solid tumors and persistently and continuously supplement O₂.Notably,assisted by NIR-II laser irradiation,the generation of O₂could be enhanced via surface plasmon resonance effect triggered,which has an ability to overcome tumor hypoxia,enhance radio sensitization,and achieve satisfactory therapeutic synergistic photothermal and radiation efficacy effect.4)In Chapter 5,intend to solve the limitations of photothermal therapy in practical clinical medical application and improve the therapeutic effect of independent photothermal therapy,such as the limited penetration depth of near-infrared laser,high expression of heat shock protein in tumor tissue,the possible inflammatory reaction and tumor cell metastasis caused by excessive temperature,we designed and constructed Pd@Au-Dox nanoplatform through significant synergy treatment with chemotherapeutic drugs and photothermal agents,used for anti-tumor hypothermia photothermal and chemotherapy combination therapy.Pd@Au-Dox sustained consistently excellent optical properties,photothermal efficiency,biocompatibility,easy surface modification and tumor passive targeted accumulation ability of Pd@Au,with chemotherapeutic drugs Dox loading to realize combined photothermal and chemotherapy therapy.