Related Experiment Video
Updated: Oct 12, 2025
Fluorescence-quenching of a Liposomal-encapsulated Near-infrared Fluorophore as a Tool for In Vivo Optical Imaging
Published on: January 5, 2015
Enzyme-activated near-infrared fluorogenic probe with high-efficiency intrahepatic targeting ability for
Yong Zhang1,2, Xueqian Chen1,2, Qing Yuan1,2
1Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology Beijing 100124 P. R. China chmsudd@bjut.edu.cn gaoxy@ihep.ac.cn.
Abstract:
Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful in situ targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe hCy-CA-LAP is converted into a high-emission hCy-CA fluorophore in the presence of LAP, showing high selectivity, high sensitivity and low detection limit (0.0067 U mL-1) for LAP, and successfully realizes the sensitive detection of small fluctuations of LAP in living cells. Moreover, the probe can achieve effective in situ accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity in vivo. Therefore, the probe hCy-CA-LAP may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI.
Insights
A new fluorescent probe, hCy-CA-LAP, effectively targets liver cells and detects drug-induced liver injury (DILI) with high sensitivity. This probe offers a promising tool for evaluating liver damage and understanding leucine aminopeptidase (LAP) roles in DILI.
Area of Science:
- Biomedical Engineering
- Chemical Biology
- Molecular Imaging
Background:
- Drug-induced liver injury (DILI) is a significant clinical challenge, necessitating improved diagnostic tools.
- Current near-infrared (NIR) fluorescent probes for liver injury exhibit limitations in targeting and sensitivity.
- Enzyme-activated probes with enhanced in situ targeting are crucial for accurate liver injury imaging.
Purpose of the Study:
- To design and synthesize a novel fluorogenic probe for sensitive and targeted detection of DILI.
- To enhance hepatocyte targeting by incorporating a cholic acid moiety into the probe structure.
- To evaluate the probe's efficacy in detecting DILI in vitro and in vivo.
Main Methods:
- Rational design of a leucine aminopeptidase (LAP) activated fluorogenic probe, hCy-CA-LAP, incorporating a cholic acid group.
- Assessment of probe selectivity, sensitivity, and detection limit for LAP.
- In situ imaging of LAP activity in living cells and evaluation of DILI models in vivo.
Main Results:
- The probe hCy-CA-LAP demonstrated high selectivity and sensitivity for LAP, with a low detection limit (0.0067 U mL-1).
- The cholic acid group significantly improved hepatocyte targeting and in situ liver accumulation.
- Precise imaging and evaluation of two distinct types of drug-induced hepatotoxicity were achieved in vivo.
Conclusions:
- The developed probe hCy-CA-LAP enables sensitive detection of LAP fluctuations in living cells.
- This probe facilitates effective in situ liver imaging for evaluating drug-induced hepatotoxicity.
- hCy-CA-LAP shows potential as a valuable tool for DILI research and assessment.
