What happens to nanoparticles when they enter the bloodstream?

Researchers have uncovered new insights into how nanoparticles behave once they enter the bloodstream, using a groundbreaking artificial circulatory system designed to mimic real-world conditions. A team led by Oya Tagit, a professor at the FHNW School of Life Sciences, developed a dynamic model that replicates the complex environment of the human circulatory system. This system allows scientists to observe how nanoparticles interact with blood proteins and cellular structures under conditions similar to those inside the body. The study, published in Advanced Materials Interfaces, focuses on the formation of a "protein corona" around nanoparticles, a layer of proteins that adhere to their surfaces upon exposure to blood. This corona plays a critical role in determining the fate of nanoparticles within the body, influencing their ability to reach target sites, avoid immune detection, and deliver therapeutic agents effectively. While much research has centered on rigid nanoparticles like gold, the study examines softer materials commonly used in drug delivery, including liposomes and polymer-based nanocarriers. The artificial circulatory system developed by the team simulates the mechanical forces and fluid dynamics present in the bloodstream, enabling detailed observations of nanoparticle behavior over time. By incorporating continuous protein exchange and mimicking the shear stresses encountered in vessels, the system provides a more accurate representation of physiological conditions than traditional laboratory methods. This innovation allows for a deeper understanding of how different types of nanoparticles respond to the body’s internal environment. In experiments involving lung cancer cells, the researchers observed that the presence of a protein corona significantly reduced the uptake of nanoparticles by cells. This finding underscores the importance of studying nanoparticles under realistic conditions, as the corona alters their physical and chemical properties, potentially affecting their efficacy and safety. Anamarija Nikoletić, a Ph.D. student and lead author of the study, noted that while all tested nanoparticles shared a common core of proteins in their coronas, there were distinct variations based on the material composition of the nanoparticles. One particularly intriguing discovery was the interaction of lipid-based nanoparticles with both soluble and membrane-bound proteins. These findings suggest that such nanoparticles may engage with extracellular vesicles secreted by cells, leading to potential fusion events that could alter their biological function. This phenomenon raises questions about how these interactions might influence the long-term stability and targeting capabilities of nanoparticles in vivo. The implications of this research extend beyond basic science, offering valuable guidance for the design of more efficient and safe drug delivery systems. By accounting for the dynamic nature of the protein corona and its impact on nanoparticle behavior, scientists can refine strategies for improving therapeutic outcomes and minimizing unintended side effects. As the field continues to evolve, the integration of advanced modeling techniques with experimental validation will remain essential for advancing nanomedicine.