Engineering Polymer-Lipid Integrated Nanoparticles with Quantitative Design Principles for Organ-Selective mRNA Delivery - PubMed
5 hours ago
- #organ-selective targeting
- #nanoparticles
- #mRNA delivery
- The study presents a quantitative design framework for organ-selective mRNA delivery using polymer-lipid integrated nanoparticles (PLINs).
- PLINs are composed of amphiphilic polyesters and cationic/ionizable lipids, expanding the chemical design space beyond conventional lipid nanoparticles.
- An I-optimal design-of-experiments (DOE) strategy was used to identify 15 formulations, enabling predictive regression models (R2 > 0.96) linking formulation parameters to organ-specific mRNA expression.
- Model-guided optimization resulted in PLINs with up to 91% lung or 96% spleen selectivity.
- Mechanistic studies revealed key physicochemical determinants of organ-tropic behaviors.
- The design rules are applicable across diverse therapeutic contexts, including genome editing, cytokine delivery, and cancer vaccination.
- The framework establishes a generalizable principle for engineering organ-targeted mRNA delivery systems.