Table 1.

Endocytosis Pathways for Nanomedicines in Tumor

Pathways	Characters	Role in Tumor
Clathrin-mediated endocytosis (CME)	Clathrin, AP2, cargo-specific adaptors, dynamin, actin are necessary. Formation of CCVs, 120 nm in an average diameter.	Mainly in charge of receptor-mediated endocytosis. Defects may be found in breast, renal and lung cancers and blood cancer like lymphomas and leukemias.
Caveolae-mediated endocytosis	Cav-1, cavin-1, dynamin and actin are necessary. Formation of caveolae, 60–80 nm in diameter.	Abundant in vascular endothelial cells, which facilitates trans-vascular endothelial cells delivery of NMs in tumor tissues. Upregulated in advanced-stage tumors. Uniformly distributed on the surface of epithelial cancer cell while absent at the apical side of confluent normal epithelial cells, which is benefit of NMs cellular entry in tumor cell.
Macropinocytosis	Clathrin-, caveolae- and dynamin-independent transient endocytosis. Formation of macropinosome in a diameter of 0.5–10 µm.	Often serve as a non-specific entry form in accompany with clathrin- and caveolae-mediated endocytosis.
Clathrin- and caveolae-independent endocytosis	Sub-classified as Arf6-, flotillin-, Cdc42- and RhoA-dependent endocytosis. Dynamin dependence is controversial. Endocytosis vesicles is 90 nm in an average diameter.	NMs entering cells via these pathways are not commonly reported. DNA-PAMAM polyplexes can achieve efficient gene delivery through flotillin-dependent endocytosis.