Exploring the Intracellular Distribution of Se Compounds Delivered by Biodegradable Polyelectrolyte Capsules Using X-Ray Fluorescence Imaging

Selenium (Se) compounds hold promise as potential therapeutics for cancer due to their diverse biological functions and redox-regulating properties. In this study, the encapsulation of a hydrophobic selenium compound inside 5 µm sized biodegradable polyelectrolyte capsules consisting of poly-L-arginine and dextran is investigated. While the encapsulated form of the compound showed comparable cellular uptake and cytotoxicity as the free drug, e.g. no improved anti-cancer efficacy is achieved, the investigation yielded crucial insights. Utilizing subcellular resolution synchrotron X-ray fluorescence imaging (XFI), the intracellular location of the Se compound is successfully visualized by demonstrating the degradation of the capsules and the following redistribution of the compound, without exogenous labeling. By applying a quantitative fitting approach, the intracellular Se mass is determined to be 0.09 ± 0.01 pg after degradation of the carrier. This highlights the potential of XFI as a powerful tool for tracking intracellular dynamics of metal-based drugs, which may facilitate drug development in the clinic.