Experimental Study Of Near Infrared Fluorescent Dye IR-783 In The Diagnosis And Treatment Of Bladder Cancer

[Background] Bladder cancer is one of the most common tumors in the urinary system,which caused great threats to the human health.In the spectrum of global diseases,the incidence of bladder cancer is among the top malignant tumors in male.Although it is reported that non-muscle-invasive bladder cancer accounts for 70% in bladder cancer,there are still many cases of bladder cancer showing muscle layer invasion at detection.Moreover,some cases already have distant metastasis and some have multiple recurrences.Therefore,early detection,early diagnosis and early treatment are the key to improve the clinical efficacy in bladder cancer.At present,cystoscopy and urinary cytology are the main methods for the early diagnosis and postoperative follow-up of bladder cancer.However,cystoscopy causes certain trauma and brings considerable pain to patients,while urinary cytology shows a relatively low sensitivity.Therefore,it is necessary to develop more specific and accurate detection methods to improve the positive rate of early diagnosis of bladder cancer.Molecular imaging,especially optical imaging,has been widely applied in clinic,and is of great value for the early diagnosis and detection of tumors including urinary tumors.Optical imaging method with high sens itivity and non radioactive safety advantages,is the main content of the research and development of molecular imaging,especially in the near infrared wavelength(650-900nm)spectral range,in which the body tissues absorption rarely.The tissue background fluorescence signal is very low.So,near infrared fluorescence imaging in tumor target is applied to the diagnosis of recent rapid development.Therefore,near-infrared probes can obtain good imaging results within the near-infrared wavelength range.IR-783,as a near-infrared fluorescent dye,specifically binds to tumor cells.Using this property,we will explore the feasibility of using IR-783 in the diagnosis and treatment of bladder cancer.[Objectives] 1.IR-783 in the near infrared fluorescence imaging of bladder cancer.2.Mechanism of near infrared fluorescent dye selective tumor imaging.3.Effect of near infrared fluorescent dyes on the biological function of bladder cancer cells.[Methods] 1.Staining of bladder cancer cells and near-infrared fluorescence imaging using near infrared fluorescent dye observe the imaging effect.2.With bladder cancer cells in the blood and urine of healthy volunteers after using near infrared dye staining and detection,in order to evaluate the near infrared fluorescence imaging in tumor cytology.3.The potential application of athymic mice to construct bladder cancer model and using near infrared fluorescent dye for imaging,in vivo imaging to assess whether near-infrared fluorescent dyes can be realized in the metabolism of bladder cancer and its distribution characteristics in vivo.4.Application of several types of organic anion transport polypeptide(O ATP)inhibitors,observation of the influence of near infrared fluorescent dyes in bladder cancer imaging,to explore the different subtypes of OATP inhibitors,inhibition of near infrared fluorescent dye uptake in tumor cells.5.Tracer is used to determine the position of organelles,observing the IR-783 combined with the specificity of the bladder cancer cell organelles,clear the IR-783 nate heterosexual absorption of organelles in tumor cells.6.Using the MTT method,the influence of near-infrared fluorescent dyes on the proliferation of bladder cancer cells was evaluated,and the toxicity of near-infrared fluorescent dyes was evaluated.7.Through cell flow,the detection of IR-783 affects the apoptosis of bladder cancer cells.[Results] 1.IR-783 has a good near infrared imaging effect in bladder cancer cells and can be well imaged at lower concentratio ns of 10umol/L.The development of.IR-783 in bladder cancer cells is more pronounced than in normal cells.2.IR-783 can detect tumor cells in blood and urine samples and can be detected even with very few cells.3.Near infrared imaging detection results of nude mouse model of bladder carcinoma confirmed by near infrared fluorescence dye showed the significance of the imaging diagnosis in bladder cancer.The main organs of the animal model were dissected and examined by near infrared imaging.It was found that the dye mainly existed in the tumor,liver and intestine.4.The study of the dye specific staining mechanism showed that the OATP1 subtype inhibited the uptake of IR-783 by bladder cancer cells most obviously.5.In the localization study of IR-783 bladder cancer cells,it is found that the dyes are mainly concentrated on the membrane organelles,lysosomes and mitochondria.6.The effect of IR-783 on cell function test showed that low concentration of dye had no obvious effect on cell proliferation,a nd high concentration of IR-783 could obviously inhibit the proliferation of cells.7.IR-783 has the effect of early apoptosis of the induced cells,and the effect is more obvious with the increase of concentration.[Conclusion] Near infrared fluorescent dye IR-783 can achieve selective bladder cancer in vivo and in vitro NIR fluorescence imaging can be used clinically for bladder cancer screening.For imaging the dose of IR-783 is low,so it will not affect the cell growth,but high concentration of IR-783 has inhibitory effect on bladder cancer.Near infrared fluorescent probe can realize the imaging diagnosis of tumors,no more use of invasive treatment,in clinical application,improve the level of diagnosis and treatment of tumors of the potential significance of the great.