Table 4.

Multiple Portals of Nanovehicle (NV) Entry as Differentiated by Cargo Chemistry and Size^* and Cell Type

	Pinocytosis
	Phagocytosis	Macropinocyto-sis	Clathrin-Mediated	Caveolae-Mediated Rafts	Lipid Rafts	Clathrin- and Caveolin-Independent
Vehicle size	a1–10 μm	a1–5 μm	<150 nm	<60 nm	40–60 nm	N/A
Actin involvement	Yes	Yes, to less extend	Yes	Yes	Yes	Yes, to less extend
Energy input	Yes	Yes	Yes	Yes	Yes/bNo	Yes
Cell types	Dendritic, macrophages, monocytes	Many cells, constitutive in some tumors	Many cells	Differentiated endothelial, adipocytes, epithelial and muscle cells	Lymphocytes, cancer cells, rodent macrophages	Specialized
Endo-lysosomal compartment	Yes, but early or late endosome arrest	By-pass or quick escape	Yes, main digestive route	By-pass or quick escape to allow for nonacidic and nondigestive route	By-pass	By-pass or quick escape; CAM-mediated uptake is strictly lysosomal
Receptor	Yes	Yes, rarely, in response to growth factors and mitogenic factors	Yes Uptake saturable	Yes; caveolae are internalised Upon activation of resident receptors Uptake saturable	Yes, rarely, nonspecific receptors (e.g., HSPG) uptake nonsaturable	Yes (e.g., IL-2 R) or nonspecific receptors (e.g., HSPG)
Adsorptive endocytosis	No	Yes	No	Yes	Yes	Yes
cFluid-phase endocytosis	+++++	++++ Uptake nonsaturable, nonspecific	++	++	++	++
dEfficiency of uptake	+++++ for specialized cells	++	+++++	+ Inefficient uptake may be offset by the lower proteolytic activity	+ Rafts are internalized constitutively	++++

^*Typically, cargo chemistry imposes itself a size range limit due to technological restrictions.

^aPhagocytosis and macropinocytosis, most likely, do not contribute to the nanovehicular uptake to a great extend.

^bBased on controversial literature entries demonstrating that the uptake of some cationic- and amphiphatic-peptide-modulated nanovehicles is energy-independent, besides a standard dependency (e.g., In Reference¹¹²). It is possible that a closer, more critical scrutiny will confirm energy-dependence of lipid-raft-mediated uptake.

^cThe extend of fluid-phase endocytosis relates to the vehicle size; estimated on scale 1–5, 5 being the highest.

^dThe efficiency of uptake may depend on NV type and chemistry. The proportion between different uptake mechanisms may vary; estimated on scale 1–5, 5 being the highest.