Fig. 7.

Schematic representation of PLA-NP internalization through clathrin-coated pits and lipid rafts in cell membrane. Endocytosis mediated by clathrin-coated pits is a fast and dynamic mechanism beginning with membrane invagination. This process involves different stages such as initiation, growth, stabilization and pit commitment, cargo capture, budding, scission and uncoating, during ~45 to ~80 s. This mechanism is dependent on proteins such as clathrin and dynamin. The diameter of coated vesicles vary from ~70 to ~135 nm, according to cell type [33]. Lipid rafts are microdomains enriched in cholesterol and sphingolipids such as sphingomyelin. Such membrane specialization is a less fluid region that compartmentalizes proteins related to intracellular signaling pathways. Planar lipid rafts can be associated to flotillins mediating endocytosis in a clathrin- and caveolin-independent manner by a still unknown mechanism [47]. In this work, we observed that PLA-NP uptake was mediated preponderantly by clathrin-coated pits and lipid rafts in A549 cells. Despite the non-alteration in cell viability, PLA-NP promoted modifications in biological functions that may affect cell physiology. IL-12 and VEGF secretion and miR155 levels were reduced while intracellular HSPs levels were increased. Such alterations may contribute to increased susceptibility to cell death