A Dual-Emissive Phosphorescent Polymeric Probe for Exploring Drug-Induced Liver Injury via Imaging of Peroxynitrite Elevation In Vivo

Abstract

Drug-induced liver injury (DILI) is a widespread clinical problem. The pathophysiological mechanisms of DILI are complicated, and the traditional diagnostic methods for DILI have their limitations. Owing to its convenient operation, high sensitivity, and high specificity, luminescent sensing and imaging as an indispensable tool in biological research and clinical trials may provide an important means for DILI study. Herein, we report the rational design and preparation of a near-infrared dual-phosphorescent polymeric probe (P-ONOO) for exploring the DILI via specific imaging of peroxynitrite (ONOO–) elevation in vivo, which was one of early markers of DILI and very difficult to be detected due to its short half-life and high reactive activity. With the utilization of P-ONOO, the raised ONOO– was visualized successfully in the drug-treated hepatocytes with a high signal-to-noise ratio via ratiometric and time-resolved photoluminescence imaging. Importantly, the ONOO– boost in the acetaminophen-induced liver injury in real time was verified, and the direct observation of the elevated ONOO– production in ketoconazole-induced liver injury was achieved for the first time. Our findings may contribute to understanding the exact mechanism of ketoconazole-induced hepatotoxicity that is still ambiguous. Notably, this luminescent approach for revealing the liver injury works fast and conveniently.

Conjugated polymer-based luminescent probes for ratiometric detection of biomolecules

“…As biosensing and bioimaging probes, their superior biocompatibility, modifiability and photo/chemical stability have also been proved. [30][31][32] In the past few years, CPderived luminescent probes have been widely utilized in superresolution imaging, multiplexed labelling, fluorescence imaging guided surgery and analysis of disease-related biomarkers. [33][34][35][36][37][38] In addition, benefitting from the many advantages of CP-based luminescent materials, such as excellent stability, ultra-high brightness and inherent and superior signal amplification capability, a variety of CP-based ratiometric probes have been developed for accurate biomolecule monitoring in a complex biological environment.…”

Red Light-Emitting Water-Soluble Luminescent Iridium-Containing Polynorbornenes: Synthesis, Characterization and Oxygen Sensing Properties in Biological Tissues In Vivo

“…Red and NIR radiation penetrates deeply into biological tissues and can be easily discriminated from the background fluorescence of the biological environment. The general approach to achieve the desirable red and NIR emission consists of incorporating cyclometalating ligands with an extended conjugated aromatic system such as 1-phenylisoquinoline, 1-(benzo[b]thiophen-2-yl)isoquinoline, 6-(benzo[b]thiophen-2-yl)phenanthridine into iridium(III) complexes [8,24]. Iridium complexes with oxygen-dependent photophysical properties (e.g., emission intensity or lifetime) are of special interest for biomedical tasks related to oxygen assessment.…”

A New Strategy: Distinguishable Multi-substance Detection, Multiple Pathway Tracing Based on a New Site Constructed by the Reaction Process and Its Tumor Targeting

“…The signaling pathway refers to a series of enzymatic reaction pathways that can transmit the extracellular molecular signals through the cell membrane into the cell to exert effects, and metabolism is one of the signaling pathways. Chemical biology requires the development of new techniques and methods to study important molecular events in the signal transduction process of living systems with chemical small molecules as probes. − With the improvement of organic synthesis technology, high performance and multifunction fluorescent probes based on organic molecules were prepared, which can not only effectively be used as a visual fluorescence tracing of signaling pathways in living systems, but can also be used as a drug for effective intervention of physiological and pathological processes: when functional molecules respond specifically, as a result of their response to the target, produces new substances to achieve intervention for life processes. − …”