The Preparation Of Gold/carbon Nanozyme And Its Application In Tumor Photothermal-reactive Oxygen Synergistic Therapy

Cancer is a disease in which the cells in the human body are uncontrolled and proliferate excessively.Although modern medical technology has been very advanced,the treatment of cancer is still one of the great puzzles for mankind.The traditional method of treating cancer not only has a difficult treatment but also causes a certain degree of damage to normal human tissues.Therefore,it is particularly urgent to find a less invasive and targeted treatment.Currently,It has been widely concerned that the emerging photothermal therapy(PTT)can convert irradiated near-infrared light into thermal energy through nanomaterials,killing tumor cells by local heating and not damaging normal tissues.Nanozymes can catalyze hydrogen peroxide and oxygen to produce large amounts of reactive oxygen species(ROS)by exerting activities such as peroxidases and oxide enzymes.Excess active oxygen can also kill cancer cells.Therefore,the aim of this study is to find a nanoscale enzyme,which has both good photothermal transformation and living oxygen,and to explore the effect of photothermal-ROS on the synergistic treatment of tumor.In this paper,we design and prepare gold/carbon composites with peroxide,oxide mimetic enzyme activity and photothermal therapy function.The effects of AuNPs and carbon layer composites,gold nanoparticle content,and other factors on the peroxygen and oxide mimic enzyme activity,stability,cytotoxicity,tumor photothermal and ROS synergistic treatment effects were systematically studied.The paper mainly includes the following three parts:(1)The nitrogen doped hollow carbon nanospheres(N-HCNs)were obtained by removing the SiO2 template with SiO2 nanoparticles as template and dopamine as carbon source.A variety of N-HCNs@AuNPs composites were prepared by loading AuNPs with different particle sizes.The morphologies and structures of the obtained materials were characterized by TEM,XRD,Raman,XPS and BET.The simulated enzymatic activity of the N-HCNs@AuNPs composite was evaluated by quantifying the UV absorbance(652 nm)produced by the substrate TMB.The Michaelis-Menten equation was used to measure the affinity between materials and substrates.The photothermal conversion performance of N-HCNs@AuNPs composites was measured by giving a certain amount of near-infrared(NIR)radiation,and the temperature rise of the system was measured.At the same time,the effects of NIR irradiation on simulated enzyme activity of N-HCNs@AuNPs composites were investigated.(2)In order to further examine the effect of gold nanoparticles on the activity of analog enzyme and photothermal transformation of gold/carbon composites,we also prepared the gold nanoparticles with yolk shell structure to load nitrogen doped hollow carbon nanospheres(Au@N-HCNs).The TEM,HRTEM,XRD,Raman,XPS,and BET were used to characterize the unique morphology and structure of the material.Subsequently,the simulated enzyme activity and photothermal conversion efficiency of Au@N-HCNs materials were studied in detail.Similarly,the size of the simulated enzyme activity was determined by catalyzing TMB coloration.The Michaelis-Menten equation was used to calculate its affinity with substrate,and ESR Pope was used to verify the formation of catalytic process in ROS.The material of photothermal conversion capabilities by calculating the thermal conversion efficiency(n)were compared.To establish the mouse subcutaneous tumor model of mouse colon cancer cell(CT26)to investigate the effect of Au@N-HCNs composite on tumor photothermal-active oxygen therapy,and preliminary bioassay of its safety:mainly including cytotoxicity tests,tumor cell uptake of the material,intracellular ROS levels,biocompatibility and in vivo distribution analysis.Compared with the previous chapter,although the photo-thermal conversion efficiency has been reduced,the gold/carbon nano-enzyme activity has been significantly improved with the reduction of the gold content.(3)Based on the above two chapters,gold/carbon nanozymes were constructed by loading multiple gold nanoparticles in a nitrogen-doped hollow carbon shell.It is expected that by increasing the amount of gold nanoparticles in the shell,the photothermal conversion efficiency of the material and the ability to generate ROS will be improved,and the effect of photothermal-active oxygen coordinated treatment of tumors will ultimately be improved.The SiO2 nanospheres were prepared by the Stober method,and SiO2 nanospheres were used as template,and 15 nm gold nanoparticles were loaded on the surface.The polydopamine was used to attach a layer of polydopamine on the surface,calcined at 800 ?,and sodium hydroxide.After immersing,the SiO2 template was removed to obtain gold-doped nitrogen-doped hollow carbon nanospheres(15 nm AuNPs@N-HCNs).In addition,2 nm AuNPs@N-HCNs were used as controls.The morphologies and structures were characterized by TEM,HRTEM,XRD,Raman,XPS and BET.Compared with N-HCNs@AuNPs materials and Au@N-HCNs materials,photothermal conversion efficiency and nano-enzyme activity of AuNPs@N-HCNs materials have been significantly improved.Animal experiments have also verified the above rules.In summary,by controlling the way of AuNPs and carbon layers,the size and content of gold nanoparticles,this paper has constructed and optimized a gold/carbon composite with excellent simulated enzyme activity and photothermal conversion performance.The material was used for tumor photothermal-reactive oxygen therapy.