The Fabrication Of Multifunctional NIR-Ⅱ Fluorescent Molecules With D-A-D-Type Structure And Their Applications In Fluorescence Imaging

The near-infrared region II(NIR-Ⅱ)fluorescence imaging with wavelengths located at 1000-1700 nm exhibits deeper tissue penetration and higher spatial resolution,due to the longer emission wavelength,less light scattering,light attenuation and tissue autofluorescence interference.The NIR-Ⅱ imaging technology has been widely used in the fields of vascular imaging,tumor imaging and surgical navigation.However,the NIR-Ⅱ fluorescent materials still face many challenges in biological applications,such as single functionality,low stability,and poor water solubility.Therefore,developing multifunctional and highly stable NIR-Ⅱ fluorescent probes is promising.This thesis firstly synthesized a water-soluble NIR-Ⅱ fluorescent molecule TTQ-F-PEG based on thiadiazolo[3,4-g]quinoxaline(TTQ-F),achieving high signal-to-noise ratios for blood vessels and fingerprints NIR-Ⅱ fluorescence and NIR-Ⅱ lifetime imaging applications.Secondly,a highly stable atom transfer radical polymerization(ATRP)initiator with NIR-Ⅱ fluorescence imaging properties was developed.It provided a platform for the development of multifunctional NIR-Ⅱ fluorescent polymers with wider applications.Finally,a multifunctional dendrimer-derived NIR-Ⅱ fluorescent polymer was prepared,which laid the foundation for the realization of NIR-Ⅱ fluorescence imagingguided photodynamic therapy(PDT).The specific contents of this thesis are as follows:(1)The development of water-soluble D-A-D structural probes and their applications in NIR-Ⅱ fluorescence/lifetime dual-modality imaging.Firstly,a water-soluble fluorescent probe TTQ-F-PEG was prepared by covalently grafting polyethylene glycol(PEG)on the side chain of TTQ-F.The probe showed good NIR-Ⅱ fluorescence imaging and lifetime imaging performance in solid and solution states.The experimental results showed that the imaging penetration depth of TTQ-F-PEG can reach8 mm.The results of in vivo imaging experiments in mice showed that the probe achieved clear NIRII fluorescence imaging and lifetime imaging of blood vessels.The fingerprint imaging chromogen was also prepared by using the solid-state luminescence properties of the probe to perform highresolution NIR-Ⅱ fluorescence /lifetime dual-modal imaging of invisible fingerprints.(2)The development of highly stable NIR-Ⅱ fluorescent molecules and their applications in atom transfer radical polymerization.In this chapter,a highly stable NIR-Ⅱ fluorescent molecule was fabricated by using the thieno[3,4-c][1,2,5]thiadiazole(TTDT)as the acceptor,9,9’-spirobi Fluorene-2(SF)as the donor.The NIR-Ⅱ fluorescent molecule composed by TTDT acceptor exhibited higher stability against alkali and redox reactions when compared with benzo[1,2-c:4,5-c’]bis([1,2,5]thiadiazole)(BBT)and quinoxaline(TTQ).More importantly,the water-soluble probe based on TTDT-SF also exhibited better anti-fluorescence quenching properties than BBT-SF and TTQ-SF.Then we synthesized a highly stable ATRP initiator based on TTDT.The initiator could efficiently initiate the polymerization of styrene and oligoethylene glycol,and the ATRP-polymerized polymers TTDT-TF-PS and TTDT-TF-POEGMA with hydrophobic and hydrophilic properties were obtained.The water-soluble polymer TTDT-TF-POEGMA had a high signal-to-noise ratio of NIR-Ⅱ fluorescence imaging in mouse blood vessels and tumors.In addition,TTDT-TF-POEGMA could be further used in NIR-Ⅱ fluorescence imaging-guided tumor resection,performing great clinical translational significance.(3)The development of D-A-D-type NIR-Ⅱ fluorescent polymer with various photodynamic properties(I/II).In this chapter,a water-soluble dendrimer PBF-AM3 with conjugated main chain of PBF and side chain of three-generation dendrimer PAMAM3 was developed.The polymer not only exhibited good water solubility,but also possessed excellent NIR-Ⅱ fluorescence imaging ability and photostability.The photodynamic characterizations showed that the introduction of dendrimers rich in tertiary amine groups greatly improved the photodynamic performance of PBF-AM3.Under the irradiation of 740 nm lasers,the polymer could simultaneously produce two different types of type I and type II ROS,which could be used for NIR-Ⅱ fluorescence imaging-guided PDT therapy.