Exploring Nanoparticle Protein Corona Integrity and Drug Distribution from Biodegradable Carriers with Synchrotron-Based Techniques

Abstract

The use of nanomaterials in medicine has increased significantly in recent years, particularly due to their unique physical and chemical properties. Their ability to bind various biological molecules, such as proteins, DNA or drugs opens therefore a wide range of possibilities in therapy and diagnostics. One of the biggest challenges in the application of nanoparticles (NPs) is the formation of the so-called protein corona. As soon as NPs are introduced in biological media different biomolecules adsorb to their surface. This biological cover influences the interactions of the nanoparticles with cells and tissues and thus determines their biodistribution,cell uptake and ultimately their efficiency and safety. The integrity of the protein corona can be influenced by various processes; therefore a deeper understanding of these changes is crucial for the development of safe and effective nanomedical applications. Furthermore, the question of how different layers of the hybrid construct 3 nanoparticle, ligands, proteins 3 can be differentiated and analyzed within these complex environments. By using traditional techniques, it is often challenging to resolve these multi-layered structures that occur in vivo. This dissertation aims to address these knowledge gaps and advance research in these areas. Specifically, the work focuses on three projects: In the first part, the integrity of a labeled pre-formed protein corona around gold nanoparticles is probed inside cells using X-ray fluorescence imaging. This study provides insight into the time dependent degradation in the intracellular environment. The second part deals with the characterization of gold nanoparticle, labeled ligands and a labeled protein corona using anomalous small angle X-ray scattering. The proof of concept shows that the method is able to distinguish between the three different parts and thus enable a more detailed analysis of the hybrid system. In the next chapter, biodegradable polyelectrolyte capsules are explored as promising carrier in the field of drug delivery. These carriers can be designed to enhance the bioavailability of hydrophobic drugs and offer controlled or triggered release properties. Understanding the behavior of these carriers within cells is crucial for optimizing their design and effectiveness. The third project explores how X-ray fluorescence imaging can be used to track the intracellular distribution of a drug delivered by biodegradable microcarriers. This focuses on the release and localization of a Selenium based drug within the cellular environment, providing important data for the development of effective and safe drug delivery systems.