In vivo imaging via a red-emitting fluorescent probe to diagnosing liver cancer or drug-induced liver disease

Yuexia Yang; Liang Zhang; Jiajun Li; Jiemin Wang; Ting Cao; Lei Zheng; Yuping Cao; Wenwu Qin; Yun Liu

doi:10.1016/j.aca.2021.338621

In vivo imaging via a red-emitting fluorescent probe to diagnosing liver cancer or drug-induced liver disease

Anal Chim Acta. 2021 Jul 11:1168:338621. doi: 10.1016/j.aca.2021.338621. Epub 2021 May 6.

Authors

Yuexia Yang¹, Liang Zhang², Jiajun Li³, Jiemin Wang¹, Ting Cao¹, Lei Zheng¹, Yuping Cao¹, Wenwu Qin⁴, Yun Liu⁵

Affiliations

¹ Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Special Function Materials and Structure Design (MOE), College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China.
² Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, PR China.
³ State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu Province, 730046, PR China.
⁴ Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Special Function Materials and Structure Design (MOE), College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, PR China. Electronic address: qinww@lzu.edu.cn.
⁵ Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, PR China. Electronic address: yunliu@tmmu.edu.cn.

PMID: 34051991
DOI: 10.1016/j.aca.2021.338621

Abstract

Leucine aminopeptidase (LAP) as an important proteolytic enzyme, has been mainly found in hepatobiliary cells, and overexpressed in hepatoma cells. Herein, a new highly selective red-emitting fluorescent probe (DCDHF-Ala) for LAP has been synthesized based on 2-dicyanomethyldiene-3-cyano-2, 5-dihydrofuran (DCDHF) as fluorophore, and alanine (Ala) as the detection group. More importantly, it's the first time to use Ala as a reactive group for LAP. DCDHF-Ala has a low detection limit (0.20 U/L), excellent water solubility and cell membrane permeability. In addition, the probe has been successfully applied to fluorescent imaging in cells and zebrafish. It's especially worth mentioning that, DCDHF-Ala has a high biosafety and enables a real-time detection of LAP levels in mice model. What's the most important is that DCDHF-Ala may be an effective tool to qualitatively monitor the upregulation of LAP induced by liver injury and liver cancer.

Keywords: In vivo and vitro; Leucine aminopeptidase; Liver injury; Mice imaging; Red-emitting fluorescent probe.

MeSH terms

Animals
Chemical and Drug Induced Liver Injury*
Fluorescent Dyes
Liver Neoplasms* / diagnostic imaging
Mice
Optical Imaging
Zebrafish

Substances

Fluorescent Dyes