Unravelling the mechanisms of nanomedicines: analytical tools to characterise the interaction between synthetic macromolecules and lipid membranes

Abstract

Polymer nanomedicines are a transformative class of therapeutics, offering tunable architectures for targeted delivery, controlled release, and improved pharmacokinetics. However, limited understanding of how these systems interact with cellular membranes, undergo internalization, and release their cargo continues to hinder their clinical translation. Membrane interactions are a key determinant of these processes yet remain underexplored in nanomedicine research. This review provides an overview of analytical techniques used to study the interaction of polymers with lipid membranes, drawing on methods from biophysics, physical chemistry, and colloid science. We introduce common model membrane systems and explain how they can complement in vitro studies. A wide range of characterization approaches are discussed, from microscopy and spectroscopy to more advanced scattering and nanomechanical techniques. By illustrating how these methods can be integrated to build a complete mechanistic understanding of dynamic interfacial behaviour, this review aims to bridge disciplinary gaps and support the development of more effective nanomedicines.