Construction And Application Of Multifunctional Organic Near-infrared-Ⅱ Fluorescent Probes

Cancer remains the world’s most deadly disease and it is therefore essential to explore effective imaging techniques and treatment strategies to tackle it.Imaging technology plays a key role in the field of cancer treatment.Compared to conventional imaging techniques,fluorescence imaging is widely used in clinical medicine due to its high sensitivity,ease of operation and high resolution.NIR-Ⅱ fluorescence imaging,with its deeper tissue penetration depth,has an outstanding performance in clinical diagnosis.In addition,compared to traditional chemotherapy and radiotherapy,emerging phototherapy techniques have been widely investigated in the medical field due to their non-invasive and non-destructive nature.Among them,photodynamic therapy(PDT)and photothermal therapy(PTT)are two typical phototherapy techniques that have attracted attention because of their low damage to normal tissues and high tumour suppression efficiency.However,PDT and PTT also have their own drawbacks,so combined treatment with PDT and PTT is considered an effective solution to improve the therapeutic effect.Combined treatment with PDT and PTT can not only induce more oxygen to enter the tumour site,thus improving the efficiency of PDT,but also inhibits the heat shock proteins during PTT,achieving a synergistic effect of PDT and PTT.Based on the above,this paper provides two new ideas on the construction of multifunctional organic NIR-Ⅱ fluorescent probes,as follows:(1)Synthesis and properties of nitro-substituted NIR-Ⅱ conjugated polymers: The effects of introducing nitro into the polymers on the properties of the materials were investigated by designing and synthesising two polymers,B-H and B-NO2.The B-H NPs and B-NO2 NPs with good biocompatibility were prepared by combining F127 with the materials through nanoprecipitation.the optical properties of the two nanoparticles,including extinction coefficient and fluorescence quantum yield,were first tested separately,followed by the photodynamic and photothermal properties of the two nanoparticles.From the absorption and fluorescence emission spectra,it was found that the BNO2 NPs with the introduction of nitro showed an absorption redshift and emission redshift compared to the B-H NPs.Furthermore,under laser irradiation,the B-NO2 NPs showed superior photodynamic effects and higher photothermal conversion(37.6%)and were therefore selected for in vitro and in vivo experiments.In cellular experiments,the nanoparticles exhibited low toxicity and excellent biocompatibility in vivo,and were able to cause severe damage to tumour cells under laser irradiation.In NIR-Ⅱ fluorescence imaging experiments,B-NO2 NPs could be enriched at the tumour and NIRII fluorescence imaging of blood vessels and tumours in vivo was successfully achieved.This study provides a new strategy for the construction of efficient NIR-Ⅱ fluorescent therapeutics.(2)Construction and application of NIR-Ⅱ organic small molecules based on atomic substitution strategy: Three organic small molecules,T-N,T-C and T-Si,were designed and synthesised by introducing nitrogen,carbon and silicon atoms.The corresponding nanoparticles were prepared by nanoprecipitation and tested for their optical properties,including solvent effect,extinction coefficient and fluorescence quantum yield of the three nanoparticles,resulting in the screening of multifunctional nanoparticles T-Si NPs with high fluorescence quantum yield(3.9%).Under laser irradiation,the T-Si NPs exhibit excellent reactive oxygen species production and excellent photothermal conversion efficiency(49.9%).In cellular experiments,T-Si NPs not only have low dark toxicity but also have a high killing rate against tumor cells under laser irradiation.In NIR-Ⅱ fluorescence imaging experiments,a significant increase in fluorescence intensity at the tumour site was observed after tail vein injection of T-Si NPs,indicating that T-Si NPs could be enriched at the tumour site and tumour localisation was achieved.This study provides an innovative idea for the construction of NIR-Ⅱ fluorescence imaging-guided PDT/PTT combination therapy.