Fig. 9.

Schematic of endocytosis (gray arrows), intracellular trafficking (blue arrows), and cellular exocytosis (red arrows) of NPs. After cellular uptake, NPs are usually delivered to early endosomes, which are the main sorting stations in endocytosis; even vesicles related to non-receptor mediated entry mechanisms fuse with early endosomes. In the early endosome, some NPs are transported along with receptors to recycling endosomes and subsequently excreted; others that remain in early endosomes move slowly along microtubules toward the cell interior and fuse with late endosomes. Finally, late endosomes fuse with lysosomes, which are not necessarily the end of the pathway; some undergo exocytosis and release their undigested content by fusion with plasma membranes. On the pathway to multivesicular bodies (MVB) or even in lysosomes, a portion of NPs may escape from vesicular compartments to the cytoplasm; in addition, some NPs may begin by entering the cytoplasm via unspecific mechanisms. NPs in the cytoplasm or trapped in vesicles can enter the nucleus, mitochondria, endoplasmic reticulum (ER), and Golgi apparatus via unknown mechanisms. In fact, vesicles containing NPs can fuse with ER, Golgi, and other organelles. NPs that enter the ER or Golgi may leave the cell via vesicles related to the conventional secretion system. NPs that are localized in the cytoplasm can leave the cells via re-entering the vesicular system or directly via unspecific mechanisms. The “question marks” in the schematic denote unknown mechanisms.