POM Dynamics in Cellular Membrane Transport (POM-DICT)

This project explores the potential of polyoxometalates (POMs)a unique class of all- inorganic metal-oxide clustersas innovative molecular carriers for drug delivery. The focus lies on two well-characterized POMs that have shown promising capabilities in transporting various therapeutic agents across biological membranes. Unlike traditional carriers such as liposomes or amphiphilic nanoparticles, POMs offer a distinct mechanism of action, driven by their ionic and highly tunable structure, enabling them to penetrate cellular barriers in a non- disruptive and selective manner. The overarching goal is to optimize the delivery performance and safety of these POMs by investigating three key aspects: (1) their interactions with diverse cargos, (2) their effects on model membranes, and (3) their behavior in different cell lines. Through these studies, we aim to establish a solid mechanistic understanding of how POMs bind, transport, and release drug molecules inside biological systems. While this research does not aim to produce a clinical drug formulation, it will provide the foundational knowledge necessary for future therapeutic applications of POM-based delivery systems. In parallel, we will investigate how POMs interact with lipid membranes that mimic the composition of cellular membranes. Using advanced techniques such as differential scanning calorimetry and X-ray scattering, we will evaluate whether and how POMs alter membrane structure and integrity. This is crucial for ensuring that drug delivery does not compromise cell viability. Finally, the project will examine the cellular uptake, localization, and safety of POMs across a panel of cancerous and non-cancerous cell lines. This will enable us to determine the specificity and potential off-target effects of these carriers and to build a comprehensive safety profile that could guide further development. Led by Prof. Annette Rompel, and supported by two PhD researchers in collaboration with Dr. habil. Ulrich Lächelt, this interdisciplinary effort combines expertise in inorganic chemistry, membrane biophysics, and drug delivery. By addressing several key knowledge gaps, the project aims to unlock the full potential of POMs as molecular transporters and lay the groundwork for their future use in targeted therapies.