Supramolecular Nanoarchitectonics Based on Antagonist Peptide Self‐Assembly for Treatment of Liver Fibrosis

Abstract Therapeutic peptides have attracted increasing attention as anti‐fibrotic drug candidates. However, the rapid degradation and insufficient liver accumulation of therapeutic peptides have seriously hampered their clinical translation. Here, the use of supramolecular nanoarchitectonics is reported to fabricate nanodrugs from therapeutic peptides for treating liver fibrosis. Self‐assembling antagonist peptides are rationally designed and manipulated into uniform peptide nanoparticles with well‐defined nanostructures and uniform sizes. Significantly, the peptide nanoparticles show enhanced accumulation in liver sites and limited distribution in other tissues. In vivo results show that the peptide nanoparticles exhibit greatly enhanced anti‐fibrotic activity compared to the pristine antagonist along with good biocompatibility. These results indicate that self‐assembly is a promising nanoarchitectonics approach to enhance the anti‐fibrotic activity of therapeutic peptides for treating liver fibrosis.