Organic nanoprobes have attracted much attention due to their tunable optical properties,good biodegradability and low toxicity.However,some probes have short excitation and emission wavelengths,which are disturbed by biological tissue scattering and autofluorescence,which is not conducive to obtaining accurate physiological and pathological information.Therefore,the development of novel long-wavelength excitation and emission organic nanoprobes is expected to overcome the problem of poor tissue penetration depth and improve the efficacy of disease diagnosis and treatment.In response to the above challenges faced by organic nanoprobes,this thesis developed organic nanoprobes with near-infrared second region(NIR-Ⅱ)fluorescence emission,which were successfully applied in the diagnosis,imaging and treatment of tumors and other diseases.The specific content is divided into the following aspects:In Chapter 2,to extend the emission wavelength of organic nanoprobes and address the poor therapeutic performance of type II photosensitizers under hypoxia,we introduced electron-withdrawing groups at both ends of the D-A’-D core to form a larger conjugated system(A-D-A’-D-A)based on the donor-acceptor-donor(D-A’-D)structure,and obtained a series of organic photosensitizers NIR-Ⅱ-X(X=H,F,Cl,Br),the absorption and fluorescence emission wavelengths are significantly red-shifted due to intramolecular push-pull electron interactions and enlargement of the conjugated system.Their corresponding nanoprobes(NIR-Ⅱ-X NPs)have good fluorescence,photoacoustic imaging properties,and photothermal effects,can generate singlet oxygen(1O2)through a highly oxygen-dependent type II mechanism,and can also generate hydroxyl radicals(·OH)through a less oxygen-dependent type I mechanism.Finally,NIR-Ⅱ-H NPs were found to have better imaging performance and photosensitivity compared with the other three probes.Our study provides ideas for the development of novel multifunctional organic nanoprobes.In Chapter 3,we selected NIR-Ⅱ-H NPs for research based on the results in the previous chapter to validate their imaging and therapeutic capabilities through in vitro and in vivo experiments.NIR-Ⅱ-H NPs exhibit excellent fluorescence and photoacoustic imaging capabilities,photothermal properties,and photosensitivity properties.In cell experiments,NIR-Ⅱ-H NPs effectively killed tumor cells through photodynamic and photothermal synergy.In in vivo experiments,NIR-Ⅱ-H NPs have long absorption and emission wavelengths and deep penetration depths,allowing high-contrast tumor images to be obtained by fluorescence imaging and photoacoustic imaging.They generate·OH through a type I photodynamic process under illumination,avoiding the limitation of tumor hypoxia,and have good photostability.Under the synergistic effect of photodynamic and photothermal,they can effectively treat subcutaneous tumors and in situ tongue cancer.NIR-Ⅱ-H NPs are expected to become an ideal nano theranostics reagent for in vivo imaging-guided therapy,and further applied to precise diagnosis and treatment of tumors.In Chapter 4,to improve the accuracy of imaging,we constructed a NIR-Ⅱ ratiometric fluorescent probe based on hypochlorous acid(HCl O)insensitive NIR-Ⅱ-H and HCl O sensitive IR1061.We studied the effects of different factors on the detection performance of the probe,and then verified its feasibility for the detection of HCl O in vitro and in vivo.The fluorescence emission range of the probe can reach the NIR-Ⅱ region,and the imaging resolution is greatly improved.After the probe reacted with HCl O,IR1061 was destroyed and the fluorescence was reduced,while the fluorescence of NIR-Ⅱ-H can be used as a reference signal,HCl O was detected according to the fluorescence intensity ratio of NIR-Ⅱ-H and IR1061,which avoided the problem of inaccurate detection results of single emission wavelength fluorescent probes.The probe not only has good detection performance,but also is not interfered by other common analytical substrates.The probe can specifically detect HCl O in inflammatory tissue and can differentiate between inflammatory tissue and normal tissue,and will become a potential ratiometric organic nanoprobe. |