Construction and Evaluation of Theranostic Near-infrared Fluorescent Probe for Targeting Inflammatory Brain Edema

doi:10.12300/j.issn.1674-5817.2023.166

Abstract

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.

Key words: Brain edema, Lipopolysaccharide, Near-infrared fluorescence, Furosemide, Theranostics, Mice

CLC Number:

R-332

Jing QIN,Yong ZHAO,Caiqin ZHANG,et al. Construction and Evaluation of Theranostic Near-infrared Fluorescent Probe for Targeting Inflammatory Brain Edema[J]. Laboratory Animal and Comparative Medicine, 2024, 44(3): 243-250. DOI: 10.12300/j.issn.1674-5817.2023.166.

Figures/Tables 5

References 29

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给药分组（n=5） Grouping and administration (n=5)	脑组织含水量/% Brain water content/%
PBS	79.511±0.483
5 mmol/L IR-783	78.364±0.949
2 mmol/L IR-783-FSM	77.988±0.124^**
5 mmol/L IR-783-FSM	77.276±0.816^**
8 mmol/L IR-783-FSM	77.364±0.949^**

给药分组（n=5） Grouping and administration (n=5)	脑组织含水量/% Brain water content/%
PBS	79.511±0.483
5 mmol/L IR-783	78.364±0.949
2 mmol/L IR-783-FSM	77.988±0.124^**
5 mmol/L IR-783-FSM	77.276±0.816^**
8 mmol/L IR-783-FSM	77.364±0.949^**

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