Triantennary GalNAc Molecular Imaging Probes for Monitoring Hepatocyte Function in a Rat Model of Nonalcoholic Steatohepatitis

Abstract

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease that can lead to irreversible liver cirrhosis and cancer. Early diagnosis of NASH is vital to detect disease before it becomes life-threatening, yet noninvasively differentiating NASH from simple steatosis is challenging. Herein, bifunctional probes have been developed that target the hepatocyte-specific asialoglycoprotein receptor (ASGPR), the expression of which decreases during NASH progression. The results show that the probes allow longitudinal, noninvasive monitoring of ASGPR levels by positron emission tomography in the newly developed rat model of NASH. The probes open new possibilities for research into early diagnosis of NASH and development of drugs to slow or reverse its progression.

Design of Hepatic Targeted Drug Delivery Systems for Natural Products: Insights into Nomenclature Revision of Nonalcoholic Fatty Liver Disease

“…268,269 This approach also provided possibilities for the early diagnosis of NASH using triantennary GalNAc molecular imaging probes. 270 Nonparenchymal hepatic cells including KCs, HSCs, and liver sinusoidal endothelial cells (LSECs) have been identified to be significantly associated with NAFLD pathogenesis. 271,272 Strategies targeting KCs include the inhibition of overactivation 273 and the regulation of the polarization of M1/ M2 KCs.…”

“…(Figure ). Another ligand GalNAc that binds to the ASGPR has been widely applied for the targeted delivery of therapeutic oligonucleotides to hepatocytes for the treatment of NAFLD or NASH. , This approach also provided possibilities for the early diagnosis of NASH using triantennary GalNAc molecular imaging probes …”

“…For example, an immunosensor based on porous-graphene-functionalized black phosphorus composite has been developed to rapidly and sensitively detect biomarkers (leptin) of NAFLD . Moreover, a bifunctional probe targeting the hepatocyte-specific ASGPR has been developed for the noninvasive monitoring of NASH progression, which provides future trends in the development of an integrated multifunctional nanoplatform for the simultaneous diagnosis and treatment of NAFLD. Second, the combined utilization of commercially available medications including natural products and western medicine has dual/multitargeted treatment effects, which augments the benefits of addressing multiple aspects of NAFLD pathogenesis .…”

Recent Progress in the Molecular Imaging of Nonalcoholic Fatty Liver Disease

“…A PET tracer was recently developed for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), which is known to become decreased as NASH progresses [ 75 ]. Liver activity and hepatocyte function could be tracked longitudinally as diet and CCl4 induced liver fibrosis development.…”

Recent research progress in galactose-based fluorescent probes for detection of biomarkers of liver diseases

“…However, in a longitudinal assessment of the response to treatment, it cannot be performed repeatedly. 22,23 Taking the drawbacks of the above traditional detection methods into consideration, to help reduce the increasing trend in liver diseases and change the status quo of liver cancer ranking fifth worldwide, the design and development of an efficient tool for the early detection of liver abnormalities is highly necessary.…”