Endogenous targeting lipid nanoparticles for systemic mRNA delivery to lung cancer tumors - PubMed
8 hours ago
- #lipid nanoparticles
- #mRNA delivery
- #lung cancer
- The study introduces novel lipid nanoparticles (LNPs) named DC_113, composed of DC-cholesterol and the ionizable lipid 113-O12B, designed for systemic mRNA delivery to lung cancer tumors.
- DC_113 LNPs have an apparent pKa above 7.9, enabling efficient interaction with plasma vitronectin (Vtn), which facilitates targeting to Vtn receptors upregulated in lung tumors.
- These LNPs selectively deliver mRNA, like follistatin (FST)-coded mRNA, to pulmonary tumors, leading to significant FST expression and inhibition of Activin A, a driver of cancer progression and cachexia.
- In an orthotopic cancer model, DC_113 achieved preferential protein expression in tumors over adjacent healthy lung tissue, reducing tumor burden approximately 2.5-fold more than liver-tropic LNPs.
- The treatment effectively mitigated cancer cachexia by improving food intake, maintaining body weight, and preserving muscle and adipose tissues without adverse effects.
- This endogenous targeting strategy enhances mRNA-based interventions for lung cancer, leveraging natural plasma components for tumor-specific delivery.