Aggregation-Regulated Long-Life Fluorescent Probes

Fluorescence imaging has been widely used in sensing clinical medical biomarkers,in-situ monitoring pathology and real-time visualization research,due to its advantages of non-invasive,good selectivity,high sensitivity and good temperal-spatial resolution.High-resolution fluorescence imaging has been successfully used to track long-term physiological processes inside organisms at a three-dimensional scale.Photodynamic therapy(PDT)is a physical diagnosis and treatment method by using light irradiation and photosensitizers.Thus,PDT has the advantages as fluorescence imaging since they both undergo the light irradiation process.In contrast to chemotherapy,surgical treatment and radiotherapy,PDT is controllable and will not cause long-term drug resistance or loss of normal tissues.As a result,PDT is a new and efficent cancer treatment,especially,when combined with other multi-line therapy strategies.The functionalization of photosensitizers allows the PDT displays targeted therapy leading to high selectivity toward special tumor cells and achieving a higher degree of lesion selectivity by applying precise light to the location of the lesion.Fluorescence probe reagents and photosensitizers are essential to fluorescence imaging and PDT therapy,respectively.Organic fluorescent molecules and photosensitizers feature good designability,tunable energy bands and good biocompatibility,which have been the hot issues for diagnosis and biosensing.Compared with traditional fluorescent probe reagents and photosensitizers,thermally activated delayed fluorescent(TADF)molecules possess unique photophysical properties,which enable them the ideal photoelectric semiconductor materials with dual functions of fluorescence imaging and photodynamic therapy.Typically,TADF emitters with the donor-acceptor structure can achieve 100%internal quantum efficiency through an efficient reverse intersystem crossing(RISC)process due to their small excited state singlet-triplet energy gap of TADF molecules.Moreover,the red and deepred emissive TADF molecules with long-lifetime triplet excited states have more potential for photodynamic therapy application by efficient triplet excited state energy transfer to oxygen or reactive oxygen species(ROS).Recently,the use of TADF materials as photosensitizers for bioimaging and photodynamic therapy has attracted more attention.In this field,fundamentally two major issues should be settled to obtain an effective TADF PSs.One is high fluorescence quantum yield of fluorophores,and the other one is the longer wavelength emission in the near infrared region.In this thesis,a series of red-light TADF molecules with D-A structure and D-A-D structure using benzopyrazine moity as the acceptor core were designed and synthesized and the corresponding water-soluble nanoparticles were also prepared by encapsulating them with amphiphilic polymers.Preliminary results proved that they had good performance in biological imaging and photodynamic effects,including:(1)Taking dibenzo[a,c]phenazine-11,12-dicarbonitrile(BPz-CN)and dibenzo[f,h]quinoxaline-2,3-dicarbonitrile(BQx-CN)as the acceptor fragment,triphenylamine as the donor moiety,the author designed and synthesized the TADF molecules named D of unilateral triphenylamine-heavy atom and bilateral triphenylamine.The results showed that the D1 molecule has the longest emission peak of 610 nm.When the author made nanoparticles by doping 50% CBP on it by means of cosedimentation,the emission wavelength was increased to 693 nm and the singlet oxygen yield reached21%.Cell experiments in vitro showed that it had good biocompatibility and photodynamic therapy,and has good intracellular fluorescence imaging and inhibitory effect on tumor cells.(2)Based on the D3 molecule containing BPz-CN fragment and bilateral triphenylamine,the author switched the positions of triphenylamine and strong electron-absorbing cyanogen group,and changed the molecular configuration from "Y type" to "T type" to obtain F1,F2 and F3 molecules,among which F1 and F2 molecules are isomers.The characterization showed that the F1 molecule had a maximum emission wavelength of 648 nm and possesses the best thermal stability,with a thermal decomposition temperature as high as 501.62 °C.The singlet oxygen yield of F1 was 37.98%,1.3times that of F2 molecule.F1 molecule was selected to prepare nanoparticles by means of coprecipitation and self-assembly with F-127.The nanoparticles had good cellular imaging effects and phototoxic effects,and provided reliable photosensitizer candidates for the construction of integrated nanoplatforms for diagnosis and treatment.The researcher selected F1,its intermediate product and F3 molecules and renamed them as FQ,FQ-Br and FQ-CN molecules.Then through horizontal comparison of experimental results of the three molecules and nanoparticles,the researcher studied the influence of heavy atoms and electron-withdrawing groups on molecular properties.The results showed that FQ-Br NPs had the strongest photodynamic effect,while FQ-CN molecule had the longest emission wavelength of 648 nm and the smallest energy gap of 0.16 e V.It showed that the adjustment strategy can effectively strengthen the spin-orbit coupling of electrons,and enhanced the effect of photodynamic therapy and imaging.