Review of ANBR by the research team of Zhen Xu and Jiang Xiqun of Nanjing University: Activated optical probes for drug-induced liver injury imaging

Abstract: The research team of Zhen Xu and Jiang Xiqun of Nanjing University systematically summarizes the application progress
of activated optical probes with fluorescence or photoacoustic imaging performance in the diagnosis of drug-induced liver injury in organisms 。 The authors classify and discuss the design and application of activated optical probes based on specific biomarkers produced during drug-induced liver injury lesions, including reactive nitrogen species (RNS), reactive oxygen species (ROS), reactive sulfur species (RSS) and enzymes.
Finally, the design of activated optical probes and the challenges faced in imaging drug-induced liver injury are presented, and the prospects
for further promoting them to clinical applications are introduced.

Keywords: activated optical probe, drug-induced liver injury, fluorescence imaging, photoacoustic imaging

Fig.
1 Different mechanisms of hepatocyte injury in drug-induced liver injury

Drug-induced liver injury (DILI), which is liver damage directly or indirectly caused by drugs or their metabolites, has become a growing public health concern
.
About 100 clinically used drugs have been reported to cause acute liver failure
.
The hepatotoxicity of most drugs was not detected prior to marketing and was subsequently withdrawn from the market
because of their risk of drug-induced liver injury.
Current clinical criteria for the diagnosis of drug-induced liver injury rely on changes in the conventional liver serum biomarker alanine aminotransferase (ALT), however, ALT levels can be affected by a variety of other conditions and may increase the risk of
false-positive signals for diagnosing drug-induced liver injury.
Therefore, there is an urgent need to develop sensitive tools to monitor pathological changes in the process of drug-induced liver injury in order to achieve early and accurate diagnosis of drug-induced liver injury
.

Optical imaging techniques, including fluorescence imaging and photoacoustic imaging, have high sensitivity and spatiotemporal resolution to visualize the physiological or pathological processes of various diseases in organisms at the molecular level
.
In order to monitor molecular states or biological events in living organisms, optical probes are essential
.
Compared with always-on optical probes, activated optical probes that produce significant signal changes in response to specific biomarkers or stimuli have attracted a lot of attention
in the field of disease diagnosis.
Therefore, activated optical probes are expected to enable early diagnosis
of drug-induced liver injury in organisms.
The research team of Zhen Xu and Jiang Xiqun of Nanjing University systematically summarized the recent research progress
of activated optical probes with fluorescence or photoimaging performance in the imaging and diagnosis of drug-induced liver injury 。 Drug-induced liver injury has multiple mechanisms, and most drugs affect liver function through three pathways, including cellular stress, mitochondrial inhibition, and specific immune responses, which disrupt mitochondrial function through intrinsic, extrinsic, or direct mitochondrial inhibition, resulting in mitochondrial permeability transition (MPT) and mitochondrial membrane rupture (Figure 1).

During cellular stress, levels of reactive oxygen species and reactive sulfur species change
with oxidation of enzymes, lipids, or nucleic acids.
Subsequently, the mitochondrial respiratory chain is inhibited, producing excess reactive nitrogen species or reactive oxygen species
.
In the presence of adenosine triphosphate (ATP), apoptosis and degradation occur, accompanied by the production of a series of enzymes; In the case of adenosine triphosphate depletion, the permeability of the mitochondrial membrane of cells increases, leading to cell necrosis and the release
of cytokines.
Therefore, changes in the levels of reactive nitrogen species, reactive oxygen species, reactive sulfur species, or enzymes during drug-induced liver injury can be used as biomarkers for the diagnosis of drug-induced liver injury
.
The authors based on different lesion-specific biomarkers during drug-induced liver injury, including reactive nitrogen species (peroxynitrite [ONOO⁻], nitric oxide [NO]), reactive oxygen species species (hydroxyl radicals [· OH], superoxide radical anion [O2^•−], hypochlorous acid [HClO], hydrogen peroxide [_H2O2]), reactive sulfur species (glutathione [GSH], hydrogen sulfide [_H2 S]) and enzymes (leucine aminopeptidase [LAP], monoamine oxidase [MAO], γ-glutamyl transpeptidase [GGT], caspase-3 [casp3], glutathione S-transferase [GST], nitroreductase [NTR]), classify activated optical probes for drug-induced liver injury imaging reported in recent years, and introduce in detail the recognition mechanism of activated optical probes in the diagnosis of drug-induced liver injury in the diagnosis of various biomarker responses, as well as their fluorescence or photoacoustic imaging applications
。 At the end of the article, the authors summarize the potential challenges of current activated optical probes for the imaging of drug-induced liver injury and the prospects for their clinical application
.

The results were published in the journal Advanced NanoBiomed Research as "Activatable Optical Probes for Fluorescence and Photoacoustic Imaging of Drug-Induced Liver Injury
.
" The first author of the article is Chen Linrong, a doctoral student at Nanjing University, and the corresponding author is Zhen Xu, a researcher at
Nanjing University.

WILEY

Paper Information:

Activatable Optical Probes for Fluorescence and Photoacoustic Imaging of Drug-Induced Liver Injury

Linrong Chen, Xu Zhen, Xiqun Jiang

Advanced NanoBiomed Research

DOI:10.
1002/anbr.
202200097

Click "Read Original" in the lower left corner to view the original text
of the paper.

Advanced

NanoBiomed

Research

Introduction to the journal

Advanced NanoBiomed Research (ANBR) aims to provide a publishing platform for nanomedicine, bioengineering and biomaterials research to improve human health, focusing on the application of these fields in the diagnosis and treatment of diseases, and hopes to become the flagship open access journal
of the Advanced series in the field of biomedicine.

AdvancedScienceNews

Wiley's official WeChat platform for scientific research information

Long press the QR code to follow us

Share cutting-edge information | focus on scientific research trends

To publish research news or apply for information sharing, please contact: ASNChina@Wiley.
com