The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes

Nanoparticles have unique capacities of interacting with the cellular machinery and entering cells. To be able to exploit this potential, it is essential to understand what controls the interactions at the interface between nanoparticles and cells: it is now established that nanoparticles in biological media are covered by proteins and other biomolecules forming a “corona” on the nanoparticle surface, which confers a new identity to the nanoparticles. By labelling the proteins of the serum, using positively-charged polystyrene, we now show that this adsorbed layer is strong enough to be retained on the nanoparticles as they enter cells and is trafficked to the lysosomes on the nanoparticles. There, the corona is degraded and this is followed by lysosomal damage, leading to cytosolic release of lysosomal content, and ultimately apoptosis. Thus the corona protects the cells from the damage induced by the bare nanoparticle surface until enzymatically cleared in the lysosomes.From the Clinical EditorThis study investigates the effects of protein corona that normally forms on the surface of nanoparticles during in vivo use, describing the steps of intracellular processing of such particles, to enhance our understanding of how these particles interact with the cellular machinery.

Graphical AbstractNanoparticles in biological fluids are covered by a biomolecular corona: using positively charged nanoparticles and labelled serum, we show that nanoparticles retain, at least in part, their corona as they enter cells and are trafficked to the lysosomes. Thanks to this layer, the cationic damage usually observed on the cell membrane for bare particles is absent and appears only later, once the corona is degraded in the lysosomes, leading to lysosomal membrane permeabilization and apoptosis. This suggests a general paradigm in which the corona protects the cells from the early interactions with the bare material.Figure optionsDownload high-quality image (106 K)Download as PowerPoint slide