The Application Of Copper Sulfide Particles For The Photothermal Therapy In Gastrointestinal Cancer

Objective:Gastrointestinal Cancer,a high trend in the world,threatens human health and results in a huge social medical burden.At present,early diagnosis and treatment,is an effective way to prevent and treat gastrointestinal cancer,combines with the rapid development of nano-probe and molecular imaging technology,is to improve the detection rate of cancer and the effective treatment of effective methods.In recent years,photothermal therapy(PTT)has become a new model of tumor diagnosis and treatment integration,showing a huge transformation of medical and clinical application potential.Recent studies have shown that copper sulfide has a high efficiency of photothermal conversion.Copper sulfide has a high signal to noise ratio of photoacoustic imaging contrast,can achieve photoacoustic imaging-phototherapy and treatment of integrated media.In this study,the photothermal effect of submicron vulcanized copper was evaluated by measuring the physicochemical properties of submicron sulfide,the effect of 980 nm near-infrared laser irradiation on the photothermal transformation efficiency of Cu S particles.The effect of copper sulfide on heat treatment was analyzed in the cell level,in vivo and by biological toxicity and safety,in order to achieve the clinical application of copper sulfide to explore new directions and application patterns,in order to achieve the integration of cancer diagnosis and treatment to explore new technologies.Methods:The four-different-size submicron grade copper sulfide powders are used for experimental investigation.The four submicron Cu S particle sizes are 80-100 nm, 100-200 nm,200-400 nm,300-600 nm,respectively.The experimental contents include the determination of submicron grade copper sulfide,studying in vitro cell experiments and in vivo experiments.1,Electron microscopic observate those Cu S particle sizes,determinate those photothermal conversion properties of those samples to observe concentration gradient and laser irradiation time on the impact of light and heat conversion temperature;determinate Cu S particles thermal stability to observe the change of light and heat conversion Efficiency.2,The effect of submicron Cu S particles on the growth of living cells was observed by CCK-8 method.The cytotoxicity of Cu S solution to colon cancer cells was observed by CCK-8 method.The cell culture medium containing different concentrations of Cu S particles was irradiated with 980 nm near infrared laser for 10 min,and the relationship between the temperature of culture medium and Cu S concentration gradient and irradiation time was observed.The apoptotic effect of Cu S photothermal effect was studied by Annexin V-FITC / PI before and after irradiation with near infrared laser.3,The GFP-Luc SW480 colon cancer cells preparate the nude mice transplanted tumor.When the tumor grows to 7mm,the tumor after injection of Cu S particles by980 nm near Infrared laser irradiation can be observed in vivo experiments,in vivo imaging,pathological sections and other methods.The absorption of submicron Cu S particles in the gastrointestinal tract of mice was observed by ICP-OES,and the toxic effects of submicron Cu S granules on the gastrointestinal tract were observed by pathological examination of mice gastrointestinal tract.Results:1,The four Cu S particle solutions are irradiated by 980 nm near-infrared laser irradiation with 0.6W/cm2,the solution temperature increases with the irradiation time,the solution temperature increases with the concentration.but temperature changes is no obvious relevance with the particle size.2,The experimental results show that the temperature rise and the heating rate of Cu S solution are consistent after repeated five times,which indicates that the submicron Cu S particles have good thermal stability.3,The Cu S particles,placed in the colon cancer cell culture medium by the 980 nm near infrared laser irradiation,was irradiated about 10 min,the thermometer temperature also measured with the Cu S liquid concentration increases,but the temperature will not continue to rise.4,The CCK-8 found that when the concentration of <200ug / ml,the sample group of cell activity rate of more than 80%;when the concentration of 400 ug / ml,the cell viability of 80-20 nm Cu S group,100-200 nm Cu S group,200-400 nm Cu S group and300-600 nm Cu S group was 70.2±1.3%,61.3±2.3%,57.9±2.01%,56.2±2.3%;when the concentration of 800ug/ml,the cell activity decreased to 40%,80-100 nm Cu S group,100-200 nm Cu S group,200-400 nm Cu S group and 300-600 nm Cu S group cell activity rate were: 38.9±8.75%、25.7±2.8%,、26.8±5.6%、56.2±3.9%.5,The expression of Cu S+HCT116+laser group was significantly higher than that of HCT116 group,Cu S+HCT116 group and HCT116+laser group by Annexin V-FITC/PI detection before and after irradiation with near infrared laser irradiation(P <0.05).6,The fluorescence imaging showed that the tumor injection of Cu S particles after980 nm laser irradiation after transplanted tumor fluorescence signal disappeared,proved to have a significant killing effect on the tumor,while the blank control group and distilled water injection control group transplant Tumor can be seen fluorescence signal.7,ICP-OES detection Cu2 +distribution showed that the contents of Cu2 +in fecal fluid,gastric tissue,small intestine and colonic tissues accounted for 57%,3%,15% and8% of Cu S,respectively,and the submicron Cu S particles Through the way into the gastrointestinal tract,most of the excrement through the form of faeces.Gastrointestinal histopathological examination showed no obvious acute inflammatory toxicity.Conclusion:1,Cu S particles have good photothermal conversion efficiency,photothermal stability,and has the good application value of photothermal therapy;2,The temperature changes is relevant to the concentration and time,but is nonrelavant to the particle size,the temperature can reach more than 42 ℃ and the temperature rise speed stable Small range,proved to have a safe and reliable clinical application potential.3,The low concentration of copper sulfide particles has no significant cytotoxicity,and can significantly kill tumor cells after near infrared radiation produced photothermal effect,the vivo experiments confirmed that the tumor tissue has a good ablation effect,It has been proved that Cu S has a good light and heat treatment effect.4,The sub-micron grade copper sulfide gastrointestinal tract after the local application of most of the excrement,the gastrointestinal tract of sub-micron grade copper sulfide particles have little absorption and pathology confirmed no significant toxicity,indicating sub-micron grade copper sulfide particles digestion Local application of this route of administration has a high safety.