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Abstract
Specific lipid compositions in lipid nanoparticles (LNPs) favor fibroblast-selective mRNA expression.
- Fibroblasts are key components of the tumor microenvironment and are diverse in function.
- Selective gene delivery to fibroblasts is difficult due to their heterogeneity and proximity to tumor and immune cells.
- A screening approach identified LNP formulations that preferentially transfect fibroblasts based on their lipid composition.
- In vitro analysis revealed that certain lipid combinations led to higher transgene expression specifically in fibroblasts, even in mixed cell environments.
- In vivo experiments showed that optimized LNPs could preferentially deliver mRNA to stromal fibroblasts in tumor-bearing mice.
- Lipid composition is a crucial factor influencing fibroblast-selective mRNA expression across various experimental models.
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