Preparation Of NIR-? Probe With Enhanced NIR-? Fluorescence For Tumor Imaging And Therapy

In the past ten years,the second near-infrared window(NIR-?,1000-1700 nm)fluorescence imaging technology,with characteristics of deep tissue penetration and low autofluorescence,has been rapidly developed.Organic NIR-? fluorescent imaging probes,which have low coxicity and can be easily modified(such as small molecule and conjugated polymer),have huge applications prospects in the biological imaging research of NIR-? fluorescence imaging.Among them,the use of active targeting technology to achieve high-brightness fluorescence imaging of tumors and other diseases has attracted wide attention from scientists.At present,the main method to improve the active targeting ability is to modify fluorophores with targeting domains(including glycosyl,RGD peptide and antibody,etc.).Although this method can effectively increase the fluorescence brightness of the fluorescent probe at the target position,the number of fluorescent probes that actually reach the target position and bind tightly to it is still extremely limited.In addition,nanomaterials with integrated diagnosis and treatment are currently a major trend in the development of nanomedicine.Among them,photothermal therapy(PTT)in the NIR-? region appears as a new way of phototherapy.Compared with traditional NIR-I(650-950 nm)PTT,NIR-? PTT displays deeper tissue penetration,less energy dissipation and less toxicity.However,most works of the current PTT are excited by light sources in the NIR-I region(for example:808 and 980 nm lasers).In response to the above two problems,this article specifically discusses the synthesis and preparation of small-molecule-based water-soluble polymer fluorescent probe.The bio-orthogonal technology is used to covalently bind the probe modified with the target molecule to the target site to specifically enhance tumor accumulation,thereby obtaining strong fluorescence and high signal-to-noise ratio NIR-? Fluorescence imaging of tumor.In addition,an organic conjugated polymer with strong NIR-? fluorescence signal was designed and synthesized by adjusting the strong new electron donor and acceptor.The NIR-? fluorescence imaging ability and imaging-guided NIR-? PTT of this conjugated polymer was further studied.The development of this work has improved the brightness,accuracy,and treatment efficiency of optical imaging probes in biomedical imaging and treatment applications.The specific researches are as follows:1.The NIR-? fluorescent probe based on bio-orthogonal technology is used for targeted fluorescence imaging of colorectal cancer.In this chapter,we first synthesized a four-arm densely grafted NIR-? fluorescent molecular probe with water-soluble polymers.In addition,through chemical grafting,the terminal groups of the probe were modified by the DBCO,which has alkynyl functional group.By studying the photophysical properties of the probe,it is found that this water-soluble polymer fluorescent probe based on NIR-? organic small molecules has desirable absorption in the NIR region,strong fluorescence in the NIR-? region,and excellent optical stability.Using bio-orthogonal technology to target this NIR-? fluorescent probe to tumor cells and solid tumors,which were pretreated with azide functional groups,the probe can effectively enrich the tumor of CT26.WT tumor-bearing mice and enhance its NIR-? fluorescence in tumor site with improved signal-to-noise ratio between tumor and liver,providing powerful tools for tumor imaging technology.Moreover,the probe can also achieve high-quality NIR-? fluorescence imaging of colorectal cancer in situ,and effectively locate in situ colorectal cancer tumors.These results indicate that using bio-orthogonal technology,the water-soluble NIR-? fluorescent probe has a good targeting effect on tumors,which can track and label tumors in a complex biopathological environment.2.Preparation of self-enhanced NIR-? fluorescent conjugated polymer by ternary copolymerization and NIR-? photothermal therapy application.This work proposes a molecular engineering technique to self-enhance the NIR-? brightness of conjugated polymers through a ternary copolymerization strategy and improve its NIR-? photothermal performance.Specifically,the NIR-? emission conjugated polymer backbone composed of a strong electron donor and a strong electron acceptor is incorporated with an additional electron donor(TC),which greatly improves the NIR-? fluorescence of the conjugated polymer.Firest,we synthesized conjugatd polymers with different TC doping ratios with self-brightening fluorescence characteristics.Then,a comparative study of their optical properties was carried out.By nanoprecipitation method,TTQ-2TC₁₂ with optimal optical properties is coated in hydrophilic polymer to prepare nanoparticles(TTQ-2TC₁₂ NPs)with good water dispersibility.TTQ-2TC₁₂ NPs displayed strong absorption at 808 nm and 1064 nm at the same time,which can satisfy bright NIR-? fluorescence imaging while achieving high-efficiency NIR-? PTT mediated by it.Through sufficient in vivo experiments(such as NIR-? fluorescence imaging of blood vessels and tumors and NIR-? PTT of tumors),it was found that TTQ-2TC₁₂ NPs can achieve bright and clear NIR-? fluorescence imaging of in vivo blood vessels and tumors and imaging-guided NIR-? PTT with deep penetration and high-efficiency to tumors.Finally,the excellent biocompatibility confirmed by histological examination and blood analysis prove the broad prospects of TTQ-2TC₁₂ NPs in future clinical applications.