Mathematical modeling and pH-sensitive Molecular Dynamics simulations of pBAE nanoparticles in mRNA delivery

Poly(beta-amino ester) (pBAE) nanoparticles are promising vehicles for mRNA delivery, particularly due to their ability to respond to pH variations in biological environments such as tumor microenvironments. In this project, we use molecular dynamics simulations to explore how pH changes influence the structure and behavior of mRNA-loaded pBAE nanoparticles. The focus is on how protonation states at neutral and acidic pH impact nanoparticle stability, compactness, and potential mRNA release mechanisms. Key properties such as conformational dynamics, surface charge, and interactions with solvent and ions are characterized. Simulations are calibrated using experimental data to support the rational design of more effective and selective delivery systems. These results aim to provide molecular-level insights into the pH-dependent behavior of pBAE systems and contribute to the optimization of nanoparticle-based mRNA therapeutics.