Molecular imaging techniques provide a favorable way for in-depth understanding of molecular biomarkers,physiological activities and anatomical structures of living organisms,and thus open up new avenues for biomedical fields and clinical research.Among various imaging technologies,optical diagnostic techniques have become effective tools for biomedical applications.Compared with visible light-near-infrared region I(400-900 nm)imaging technology,near-infrared region Ⅱ(NIR-Ⅱ,1000-1700 nm)fluorescence imaging technology can significantly reduce background autofluorescence and biological tissue light scattering.These properties bring the advantage of higher tissue penetration depth,higher temporal and spatial resolution,and improved overall imaging quality,making it a critical player in biomedical research.Photothermal therapy(PTT)is a non-invasive and highly effective cancer treatment that uses photothermal converter agents to convert absorbed laser energy into thermal energy to eliminate malignant tumors.Compared with inorganic photothermal materials,organic photothermal materials can be structurally modified to adjust their physical and chemical properties,so that they have good biocompatibility,stability and high photothermal conversion efficiency.Organic photothermal agents have been widely designed for optical diagnosis and treatment.Based on this,this research provides a scheme for NIR-Ⅱ fluorescence imaging-guided photothermal therapy.The objective of this research was to ameliorate the disadvantages of current organic photothermal agents,including poor water solubility,limited tumor aggregation,low bioavailability,photobleaching and low photothermal efficiency.Organic small molecule probes usually have large molecular weights and poor tumor permeability,and are not easily metabolized.We propose to develop a small molecular weight highly efficient photothermal agent with rapid metabolism in vivo,which can effectively combine NIR-Ⅱ imaging and photothermal therapy.In this thesis,a novel small molecule diagnostic probe,SeC-NPs,was designed and synthesized,based on donor-donor-donor type(D-A-D)chemical molecular backbone commonly used for organic small molecule dyes.The main research findings are summarized as follows:an electron donor was introduced at the electron acceptor of[1,2,5]selenadiazolo[3,4-f]-2,1,3-benzothiadiazole to obtain the target compound SeC,and the water solubility was increased by encapsulating SeC with DSPE-PEG2000 to form nanoparticles SeC-NPs.The maximum absorption wavelength of SeC-NPs in water is about 795 nm and the maximum emission is at 950 nm,and the measured photothermal conversion efficiency is as high as 62%.The CCK-8 cytotoxicity test and live/dead cell staining test proved that SeC-NPs had the effect of killing cancer cells.In addition,SeC-NPs have the capability of NIR-Ⅱ imaging,and the hindlimb vessels of mice was imaged with a signal-to-noise ratio(SBR)of 1.33 at five minutes.Plasma half-life was also measured and SeC-NPs exhibited a short blood retention time with a plasma half-life of 3.32 h.A 4T1 subcutaneous tumor animal model was established to determine the optimal time point for photothermal therapy by NIR-Ⅱ tumor imaging.The results of in vivo anti-tumor photothermal therapy experiments showed that SeC-NPs efficiently inhibited tumor growth under 808 nm laser irradiation without significant damage to normal tissues,demonstrating the good biocompatibility and excellent photothermal therapeutic effect of SeC-NPs.The in vivo biosafety of SeC-NPs was further confirmed by subsequent 7-day acute toxicity experiments and in vivo metabolism. |