# Peptide-Functionalized Liposomal Nanocarriers for Targeted Therapy of Liver Fibrosis and Hepatocellular Carcinoma: Design, Mechanisms, and Clinical Prospects

## TL;DR

This review explores how peptide-functionalized liposomes can improve targeted drug delivery for liver diseases like fibrosis and cancer.

## Contribution

The paper provides a comprehensive analysis of design strategies and targeting mechanisms for peptide-guided liposomal nanocarriers in liver disease.

## Key findings

- Peptide-functionalized liposomes enhance drug delivery to specific liver cells.
- Preclinical studies show reduced fibrosis markers and tumor growth suppression.
- Challenges include receptor heterogeneity and manufacturing scalability.

## Abstract

Liver fibrosis and hepatocellular carcinoma (HCC) remain
major
global health burdens, in part due to limited drug specificity, off-target
toxicity, and the complex hepatic microenvironment. Peptide-functionalized
liposomal nanocarriers have emerged as a promising approach to enhance
cell-selective drug delivery to activated hepatic stellate cells in
fibrosis and malignant hepatocytes in HCC. This review critically
examines recent progress in peptide-guided liposomal systems, focusing
on design strategies, receptor-mediated targeting mechanisms, and
translational considerations. Key peptide ligands, including cyclic
RGD peptides targeting integrins αvβ3/αvβ5,
GE11 for epidermal growth factor receptor, and transferrin receptor-binding
peptides, are discussed in relation to their roles in promoting receptor-mediated
endocytosis. Liposome fabrication methods and ligand conjugation chemistries
are evaluated for their impact on stability, ligand presentation,
and in vivo biodistribution. Preclinical evidence demonstrating improved
drug accumulation, reduced fibrosis markers, and suppression of tumor
growth is summarized alongside current limitations including receptor
heterogeneity, extracellular matrix barriers, and manufacturing scalability.
Finally, emerging directions such as stimuli-responsive and theranostic
liposomes as well as combination strategies with immunomodulatory
therapies are highlighted. By integrating mechanistic insight with
design and translational perspectives, this review identifies key
opportunities and the remaining hurdles in advancing peptide-targeted
liposomal nanomedicines for liver disease.