Bioconjugate chemistrySep 16, 2025

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

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

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.

Simplified

For siRNA-based therapeutics that require repeated administration, the accumulation of ionizable lipids in the body could causesafety issues. In the present study, we examined the feasibility of a bile acid-histidine decapeptide (H10) conjugate as a novel, biocompatible, and potential additive to reduce the proportion of ionizable lipids for the formulation of LNPs. A lithocholic acid (LCA)-H10 conjugate (LH conjugate) was synthesized and incorporated into the LNPs with low proportions of ionizable lipids (LiLNPs). The fabricated LH conjugate-containing LiLNPs (LiLNP-LH) exhibited more promising gene silencing activity than LiLNPs, despite their similar particle size and morphology. Additionally, LiLNP-LHs exhibited an elevated liver accumulation after intravenous injection and significantly decreased release of the inflammatory cytokines, compared with conventional LNPs with high proportions of ionizable lipids (HiLNPs). Thus, we successfully reduced the proportion of ionizable lipids in LNPs by adding LH conjugates, which could serve as carriers for diverse siRNA therapeutics with promising silencing activity and superiorsafety. in vivo in vivo

Full Text

Full text is available at the source.

View Full Text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief