Lanthanide Complexes Enhanced Emission Of Cyanine Dyes In The Second Near-Infrared Region And Their Application In Vivo Fluorescence Imaging

Vivo fluorescence imaging technology can assist biomedical diagnosis and treatment,especially in the second near-infrared region（NIR-II）.Compared with the traditional visible region and the first near-infrared region,NIR-II imaging has the advantages of high signal-to-noise ratio,high resolution imaging and deep tissue penetration depth.At present,the organic small molecular dyes and polymer fluorescent probes for NIR-II imaging have the defects of poor water solubility,poor light stability,easy aggregation quenching in aqueous solution,and long-term safety problems that are difficult to completely metabolize out of the body.In this paper,by combining the lanthanide complex with cyanine dye IR-808,a novel NIR-II polymer fluorescent probe with good water-soluble,bright fluorescence imaging effect and fast metabolism ability was synthesized.Firstly,we designed IR-808 monomer and complex monomer,which were combined with oligoethylene glycol methacrylate（OEGMA）by the copolymerization of reversible addition-fragmentation chain transfer polymerization（RAFT）.The fluorescent probes P-(OEGMA₄₀-co-Dye_0.05-co-（Ln-DO3A）₃)and P-(OEGMA₄₀-co-Dye_0.05-co-（Ln-DTPA）)were prepared.The IR-808 dye was evenly distributed on the main chain by polymerization,which effectively avoided the aggregation and quenching of the dye in aqueous solution.Moreover,the emission intensity of IR-808 dye was significantly increased by the introduction of different lanthanide complexes,which might be produced by the energy transfer from the 4f-4f energy level transition of the lanthanide complex to IR-808.We found that Ho³⁺complex had the strongest effect on IR-808 emission enhancement,so P-(OEGMA₄₀-co-Dye_0.05-co-（Ho-DTPA）)was selected for vivo fluorescence imaging.P-(OEGMA₄₀-co-Dye_0.05-co-（Ho-DTPA）)was injected into the caudal vein and metabolized rapidly through the hepatobiliary system and kidney,the fluorescence signal of the main organs almost disappeared within 6 h.In addition,biocompatibility evaluation showed that polymer fluorescent probe was safe in vivo.The NIR-II polymer fluorescent probe had excellent optical properties and great clinical application potential in imaging and surgical guidance of kidney and hepatobiliary system diseases.