Hepatic Stellate Cell Targeting Using Peptide-Modified Biologicals

Ruchi Bansal*, Klaas Poelstra*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

3 Citations (Scopus)

Abstract

Liver diseases are a leading cause of death worldwide and are rising exponentially due to increasing prevalence of metabolic disorders. Hepatic stellate cells (HSCs) are recognized as a key therapeutic target in liver diseases as these cells, upon activation during liver damage and ongoing liver inflammation, secrete excessive amounts of extracellular matrix that leads to liver tissue scarring (fibrosis) responsible for liver dysfunction (end-stage liver disease) and desmoplasia in hepatocellular carcinoma. Targeting of HSCs to reverse fibrosis progression has been realized by several experts in the field, including us. We have developed strategies to target activated HSCs by utilizing the receptors overexpressed on the surface of activated HSCs. One well-known receptor is platelet derived growth factor receptor-beta (PDGFR-β). Using PDGFR-β recognizing peptides (cyclic PPB or bicyclic PPB), we can deliver biologicals, e.g., interferon gamma (IFNγ) or IFNγ activity domain (mimetic IFNγ), to the activated HSCs that can inhibit their activation and reverse liver fibrosis. In this chapter, we provide the detailed methods and the principles involved in the synthesis of these targeted (mimetic) IFNγ constructs. These methods can be adapted for synthesizing constructs for targeted/cell-specific delivery of peptides/proteins, drugs, and imaging agents useful for various applications including diagnosis and treatment of inflammatory and fibrotic diseases and cancer.

Original languageEnglish
Title of host publicationHepatic Stellate Cells
Subtitle of host publicationMethods and Protocols
Place of PublicationNew York, USA
PublisherHumana Press
Chapter17
Pages269-284
Number of pages16
ISBN (Electronic)978-1-0716-3207-9
ISBN (Print)978-1-0716-3206-2
DOIs
Publication statusPublished - 30 May 2023

Publication series

NameMethods in Molecular Biology
Volume2669
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Chemical conjugation
  • Hepatic stellate cells
  • HSCs targeting strategies
  • PDGFR-β
  • Receptor targeting peptides
  • Targeted biologicals
  • NLA

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