Peptide-Modified Albumin Carrier Explored as a Novel Strategy for a Cell-Specific Delivery of Interferon Gamma To Treat Liver Fibrosis

Excessive accumulation of the extracellular matrix proteins primarily produced by activated hepatic stellate cells (HSC) leads to liver fibrosis. To date, no successful therapeutic intervention is available for the treatment of this disease. Platelet derived growth factor beta receptor (PDGFβR) is highly upregulated on disease-inducing activated HSC and thus can be used for delivery of antifibrotic drugs to increase therapeutic efficacy with reduced adverse effects. Interferon gamma (IFNγ) has been recognized as a potent antifibrotic cytokine; however, poor pharmacokinetics and side effects due to frequent administration have limited its clinical use. For HSC-specific delivery, a PDGFβR-specific drug delivery carrier (PPB–HSA) was developed by modifying albumin with PDGFβR-recognizing cyclic peptides. Subsequently, IFNγ was conjugated to PPB–HSA via bifunctional PEG linkers to synthesize PPB–HSA–PEG–IFNγ. In vitro, PPB–HSA–PEG–IFNγ retained complete biological activity similar to unmodified IFNγ and showe...