# Development of engineered magnetic liposome/exosome hybrid as a novel caffeine nanocarrier for restraining liver fibrosis induced in rats

## TL;DR

Researchers developed a caffeine-loaded magnetic hybrid nanoparticle to target liver fibrosis in rats, showing improved liver function and reduced inflammation.

## Contribution

A novel caffeine nanocarrier combining exosomes and magnetic liposomes for targeted liver fibrosis treatment was developed and tested.

## Key findings

- The exosome-Caff/SPION liposome hybrid (F1) showed the best results in improving liver function markers and reducing inflammation.
- F1 outperformed other formulations in restoring liver histoarchitecture and hepatocyte proliferation.
- The hybrid formulation effectively targeted injured liver tissue, suggesting a new treatment strategy for liver fibrosis.

## Abstract

Liver fibrosis, a severe health issue linked to liver injury, inflammation, and cell death, often progresses to liver cancer without effective treatments. In this study, an exosome-nanoliposome hybrid loaded with caffeine (Caff) was developed for the management of liver fibrosis. The role of superparamagnetic iron oxide nanoparticles (SPION) in promoting targeted delivery to the liver was also investigated. Caff-loaded liposomes with variable phospholipid and stearylamine molar ratios were prepared and characterized. The formula with optimized characteristics (Caff/liposomes) selected by Design Expert exhibited a particle size of 179.73 ± 3.1 nm, a polydispersity index of 0.19 ± 0.02, an entrapment efficiency of 89.79 ± 21%, and a zeta potential of -35.50 ± 1.1 mV, and was used to encapsulate SPION. Caff/SPION liposomes were further loaded into exosomes, isolated from bone marrow-mesenchymal stem cells, and visualized by TEM. The biological experiment was conducted on rats with thioacetamide-induced liver injury to reveal the efficacy of exosome-Caff/SPION liposome hybrid (F1) in comparison to exosome-Caff/liposomes (F2) and exosome-SPION/liposomes (F3). Among all the tested formulations, F1 demonstrated the most promising results regarding liver function markers (ALT and AST), inflammatory molecules (IL-6, IL-10, TLR-4, Myd88, NF-κB), fibrotic protein (α-SMA), hepatocyte proliferative capacity (PCNA), as well as liver histoarchitecture. This finding suggests that the engineered Caff/SPION liposome-exosome hybrid can effectively enhance the targeting of the drug and the homing of exosomes to the injured liver, thereby representing a novel strategy for treating liver fibrosis.

The online version contains supplementary material available at 10.1038/s41598-025-31169-w.