实验动物与比较医学2024，Vol.44Issue(3)：243-250,8.DOI:10.12300/j.issn.1674-5817.2023.166
靶向炎性脑水肿的诊疗一体化近红外荧光探针的构建与评价
Construction and Evaluation of Theranostic Near-infrared Fluorescent Probe for Targeting Inflammatory Brain Edema
摘要
Abstract
Objective A novel compound based on near-infrared fluorescence(NIRF)probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects through in vivo imaging.Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide(FSM)to obtain the new compound,IR-783-FSM.The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer.The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments.Its cytotoxicity was evaluated through CCK8 assays.A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide(LPS),confirmed by HE staining and dry-wet weight methods for brain tissues.The mice in the brain edema model were divided into control group,IR-783,and IR-783-FSM treatment groups,receiving intraperitoneal injections of PBS,IR-783,and IR-783-FSM,respectively.Real-time in vivo fluorescence imaging was then performed.The mice in each group were euthanized after 10 hours.Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model.Results The newly synthesized compound,IR-783-FSM,retained the excellent near-infrared fluorescence characteristics of IR-783.It could target mouse macrophages with an IC50 of 48.82 μmol/L.A brain edema model could be successfully constructed with intraperitoneal injection of LPS,with significantly higher brain tissue water content compared to the control group(P＜0.01).In vivo imaging showed that IR-783-FSM had a significantly stronger fluorescence signal in the brain edema model than IR-783.Compared to the control group,the brain water content was significantly reduced in the 2,5,and 8 mmol/L IR-783-FSM treatment groups(P＜0.01).Conclusion The newly synthesized NIRF probe IR-783-FSM facilitates dynamic monitoring of brain edema and real-time evaluation of therapeutic effects.关键词
脑水肿/脂多糖/近红外荧光/呋塞米/诊疗一体化/小鼠Key words
Brain edema/Lipopolysaccharide/Near-infrared fluorescence/Furosemide/Theranostics/Mice分类
医药卫生引用本文复制引用
秦靖,赵勇,张彩勤,白冰,师长宏..靶向炎性脑水肿的诊疗一体化近红外荧光探针的构建与评价[J].实验动物与比较医学,2024,44(3):243-250,8.基金项目
军队实验动物专项科研课题"靶向性近红外荧光探针在损伤性脑水肿模型评估与治疗中的应用"(SYDW[2020]21号) （SYDW[2020]21号）
陕西省创新能力支撑计划"创伤性脑水肿模型的制备及影像学实时监测评估"(2022PT-45) （2022PT-45）
