Figure 1.

Schematic graph of the endocytosis pathways of nanomedicines (NMs). NMs enter cells through different endocytosis pathways, including clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis, clathrin- and caveolae-independent endocytosis (Arf6-, flotillin-, Cdc42- and RhoA-dependent endocytosis), macropinocytosis and phagocytosis. In all the pathways, NMs following the fundamental steps. i) Binding and budding. NMs interact with cell surface through non-specific interactions and are subsequently engulfed in the cell membrane to form invaginations; ii) Pinching off. Membrane invaginations are pinched off to form different endocytic vesicles (clathrin-coated vesicles (CCVs), caveosomes, GPI-anchored protein-enriched early endosomal compartment (GEEC), macropinosome and phagosome). iii) Sorting and intracellular trafficking. Endocytic vesicles infuse into early endosomes, which act as a sorting machine and can carry the cargos to different destinations, such as lysosome, recycling endosome and subcellular organelles as illustrated in the graph.