The role of natural processes and surface energy of inhaled engineered nanoparticles on aggregation and corona formation.

The surface chemistry of engineered nanoparticles (ENPs) becomes more important as their size decreases and enters the nanometer-range. This review explains the fundamental properties of the surface chemistry of nanoparticles, and argues that their agglomeration and the formation of corona around them are natural processes that reduce surface energy. ENP agglomeration and surface corona formation are further discussed in the context of inhaled ENPs, as the lung is a major port of ENP entry to the body. The pulmonary surfactant layer, which the inhaled ENPs first encounter as they land on the lung surface, represents a unique environment with a variety of well-defined biomolecules. Many factors, such as hydrophobicity, surface charge of ENPs, protein/phospholipid concentrations of the alveolar lining fluid, etc. influence the complex processes of ENP agglomeration and corona formation in the alveolar lining fluid, and these events occur even before the ENPs reach the cells. We suggest that molecular dynamic simulations can represent a promising future direction for research of the behavior of inhaled ENPs, complementing the experimental approaches. Moreover, we want to remind biologists working on ENPs of the importance relationship between ENP surface energy and size.