Proceedings of the National Academy of Sciences of the United States of AmericaMay 29, 2026

Using mRNA-packed nanoparticles to create immune cells in the liver that reduce scarring by blocking scar-forming cells and adjusting the immune environment

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Updated May 30, 2026

Abstract

The therapeutic approach utilizing CD163 antibody-conjugated liposomal nanoparticles led to a significant reduction of extracellular matrix in liver fibrosis.

Myofibroblasts, derived from hepatic stellate cells and portal fibroblasts, are key contributors to the buildup of extracellular matrix in liver fibrosis.
Fibroblast activation protein (FAP) is highly expressed in activated hepatic stellate cells and is crucial in the development of liver fibrosis.
The study explored a method to deliver FAP-specific chimeric antigen receptor macrophage mRNA using liposomal nanoparticles targeted at liver macrophages.
Transduction of macrophages with these nanoparticles enhanced their ability to engulf and eliminate target cells.
This approach may help in resolving liver fibrosis by targeting and neutralizing overactive fibroblasts.

Simplified

Liver fibrosis, marked by an abnormal buildup of extracellular matrix (ECM), poses a major health threat. Myofibroblasts, predominantly derived from hepatic stellate cells (HSCs) and portal fibroblasts, are the primary drivers of ECM synthesis. Fibroblast activation protein (FAP), highly expressed by activated HSCs, is a pivotal player in the pathogenesis of liver fibrosis. Delineating the mechanisms underlying HSC activation and devising strategies to curb their hyperactivity are paramount for the management and prevention of liver fibrosis. In this study, we explored a pioneering therapeutic approach leveraging CD163 antibody-conjugated liposomal nanoparticles (LNPs) encapsulating FAP-specific chimeric antigen receptor macrophage (CAR-M) mRNA (αCD163/LNP-FAPCAR). These LNPs are designed to selectively transduce liver macrophages, facilitating the in situ generation of FAP-specific CAR-modified macrophages (FAPCAR-M). Our findings revealed that these LNPs efficiently transduced macrophages, augmenting their phagocytic capabilities toward target cells. This resulted in a significant reduction of ECM and a concomitant enhancement of liver fibrosis resolution. The overarching goal is to precisely target and neutralize hyperactive fibroblasts, offering a promising avenue for treating liver fibrosis.

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Competing interests

Competing interests statement:The authors declare no competing interest.

PubMed

Using mRNA-packed nanoparticles to create immune cells in the liver that reduce scarring by blocking scar-forming cells and adjusting the immune environment

Abstract

Full Text

Funding

Competing interests

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