Applications Of Near-Infrared Cyanine Nanoprobes In Protein Detection And Tumor Theranostics

Cyanine dyes and derivatives with the characteristics of wide spectral range,high fluorescence quantum yield,and easy structure modification,have been widely used for near-infrared(NIR)fluorescence imaging and phototherapy.However,the poor photostability and water solubility hinder their biomedical applications.Therefore,the design and synthesis of functionalized cyanine dye molecules with improved physical and chemical properties is a research hotspot.In this thesis,by introducing the conjugated groups,NIR cyanine dyes were used as the maternal structure to obtain new cyanine dyes.Afterwards,the cyanine dye-based nanoprobes were prepared for albumin detection and cancer theranostics.The main content included:(1)Fluorescent"off-on"cyanine nanoprobe(LNP)for serum albumin detection in urineThe tertiary pyridine group was used to modify the central substituent of the precursor IR-823 dye,thus synthesizing a dual-wavelength(610 and 840 nm)fluorescent molecular probe(LET-6).Using nanoprecipitation method,LET-6 and amphiphilic polymer(DSPE-PEG2000)were assembled to prepare nanoprobe(denoted as LNP).The probe can specifically detect albumin.According to the change of fluorescence emission intensity at 610nm,the detection limit of albumin is calculated 70.6 n M.Based on isothermal titration experiments and molecular docking simulations,it is proved that there is strong interaction between LET-6 and albumin,which is the main reason for the fluorescence recovery.The probe is not disturbed by various body fluid environments,and can achieve quantitative detection of urine albumin content in a mouse model of acute kidney injury.(2)Iron-chelated cyanine nanoprobes(ITF NPs)for photothermal-enhanced chemodynamic therapy of tumorThe organic complex([IR-TPy]Fe²⁺)was obtained by the pyridine modified IR-823 dye chelated with the divalent iron ion(Fe²⁺).Then[IR-TPy]Fe²⁺and amphiphilic polymer(DSPE-m PEG2000)were assembled to prepare iron chelation Cyanine nanoprobes(ITF NPs).After intravenous injection of ITF NPs,it can efficiently accumulate in the tumor site and can be used for fluorescence/photoacoustic dual-modality imaging of tumor.Under NIR laser irradiation,photothermal-enhanced chemodynamic therapy of tumor was achieved by the exposure of Fe²⁺in the nanoprobe.In this thesis,by the structure modification of NIR cyanine dyes,functionalized cyanine dye-based nanoprobes were successfully prepared for albumin detection and cancer theranostics.This study provides new solutions and methods for the biomedical application of NIR cyanine dyes.