Bile Acid–Histidine Decapeptide Conjugates as Promising Additives in Lipid Nanoparticle Formulation for siRNA Delivery

Sep 16, 2025Bioconjugate chemistry

Bile acid-linked small peptides as helpful additives in lipid nanoparticles for delivering siRNA

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Abstract

The lithocholic acid-histidine decapeptide conjugate reduced ionizable lipids in liposomal nanoparticles while enhancing gene silencing activity.

  • The LH conjugate was synthesized and incorporated into liposomal nanoparticles (LiLNPs) with low ionizable lipid content.
  • LiLNPs containing the LH conjugate (LiLNP-LH) demonstrated improved gene silencing activity compared to standard LiLNPs.
  • LiLNP-LHs showed increased liver accumulation following intravenous injection.
  • LiLNP-LHs significantly reduced the release of inflammatory cytokines compared to liposomal nanoparticles with higher ionizable lipid proportions.

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