Luminescence Imaging of Acute Liver Injury by Biodegradable and Biocompatible Nanoprobes

Abstract

Liver injury can result in different hepatic diseases such as fatty liver, liver fibrosis, hepatitis, and liver failure, which are mainly responsible for global mortality and morbidity. Early diagnosis is critical for the treatment of liver diseases. Herein we report luminescence imaging of neutrophil-mediated acute liver injury, including alcoholic liver injury (ALI) and acute liver failure (ALF). To this purpose, a biodegradable luminescent material was developed by chemical functionalization of a cyclic oligosaccharide, which can be produced into nanoprobes (defined as LaCD NPs). Luminescence of LaCD NPs was dependent on the level of reactive oxygen species and myeloperoxidase (MPO). Correspondingly, activated neutrophils could be specifically imaged by LaCD NPs, and the luminescent signal was positively associated with the neutrophil count. In mouse models of ALI and ALF, LaCD NPs enabled precise quantification and tracking of neutrophils in livers. In both cases, changes in the luminescence intensity are consistent with time-dependent profiles of neutrophils, MPO, and other parameters relevant to the pathogenesis of liver injury. Moreover, the luminescence imaging capacity of LaCD NPs can be additionally improved by surface functionalization with a neutrophil-targeting peptide. In addition, preliminary in vitro and in vivo studies demonstrated good safety of LaCD NPs. Consequently, LaCD NPs can be further developed as an effective and biocompatible luminescent nanoprobe for in vivo dynamic detection of the development of neutrophil-mediated acute liver injury. It is also promising for diagnosis of other neutrophil-associated liver diseases.

Untapped toolbox of luminol based polymers

“…LUM-IMI-CD, displayed amphiphilic properties since the covalently linked luminol units were relatively hydrophilic, whereas the remained imidazole moieties were hydrophobic. Analytical characterization based on NMR spectroscopy and 77 Poly(ethylene glycol) (PEG), as a non-natural biocompatible polymer, is widely used as a gold standard from industrial manufacturing to medicine-oriented research, and therefore it was of crucial importance to deliver a PEG-based system which is modified with a luminol derivative. Accordingly, Zhang and colleagues have synthesized an amphiphilic polymeric conjugate of PEG (i.e.…”

Cell‐Based Bio‐Hybrid Delivery System for Disease Treatments

“…The recruitment and infiltration cascade of neutrophils are initiated by the endothelium following the gradient of inflammatory factors like cytokine and chemokine. Therefore, neutrophil is usually taken as an indicator of inflammation and relevant diseases, [ 34–37 ] and has been widely studied as a drug delivery system in recent years. [ 38 ] For example, neutrophil‐based delivery system can cross the blood–brain barrier (BBB) and overcome the blood–brain–tumor barrier (BBTB) for malignant glioma treatment.…”

The Vibrant Interplay of Light and Self‐Reporting Macromolecular Architectures

“…Furthermore, those spherical nanoparticles self‐illuminated alcoholic liver injury and acute liver failure under diseased conditions. [ 74 ]…”