Design,Synthesis,and Characterization Of Near-infrared Light Absorptive Organic Fluorescent Dyes For Biomedical Application

Near-infrared-triggered organic fluorescent dye are widely used in biological sensing, fluorescent and photoacoustic imaging, drug delivery, and photodynamic therapy and has becoming the focus of biomedical research which attribute to good organic photoelectric characteristics, features of easy to modify, and good biocompatibility. First, near-infrared light with deep tissue penetration capability, would not cause damage to normal tissues and cells. And substances contained in the organism with poor absoption or scattering in near infrared region would help to reduce the interference of background fluorescence in the process of imaging. Second, the structural diversity of organic fluorescent dyes facilitate the introduction of various functional groups. Such as targeting or drug molecules, light sensitive groups, and water-soluble functional groups, which could realize multifunctional organic fluorescent dyethat we needed. Based on this principle, we designed and synthesized a series of organic fluorescent material response to near infrared light. And then their fundamental photophysical properties, self-assembly behavior, photo degradable and the ability to produce singlet oxygen was studied. At last, BODIPY NPs low toxicity and good biocompatibility were used for photoacoustic imaging(PAI) and photodynamic therapy(PDT) in vitro.(1) A novel photosensitive water-soluble cationic polymer(PPE-NB-PEG) was designed and synthesized. The positive charges were studied after quaternary ammoniation with photodegradable ONB group. The zata potential was also measured after photodegradation of ONB. The results demonstrated that zeta potential decreaed with the prolonged irradiation time because light-switchable polymer sidechain could be cleaved from cationic to zwitterionic.(2) A new two-photon-triggered degradable amphiphilic copolymer was synthesized in which photo-cleavable species ONB was positioned alternately into the backbone of(phenylethynyl)benzene(PPE) based polymer. Further, PEG was grafted to the side chain of copolymer to obtain water-solubility(PPE-ONB-PEG). Its fundamental photophysical properties, self-assembly behavior(particle size, morphology) and photo degradation were studied. The results showed that the self- assembly micelles could dissociate under 800 nm irradiation and Nile Red encapsulated in the micelles could be successfully released.(3) A novel BODIPY NPs was designed and synthesized. The photophysical properties, photoacoustic signal and the ability to induce singlet oxygen in physiological environment was studied. Experimental results showed that the photostability and the ability to generate singlet oxygen were better than the commercial photosensitizer(ICG). Finally, we use MTT method to verify the low cytotoxicity of BODIPY NPs. The photoacoustic imaging showed that the material is mainly enriched in lysosomes after incubated with cells. The PDT results showed that BODIPY NPs can kill A549 cells after appropriate irradiation which futher affirmed the potential applications of BODIPY NPs in biomedical field.