Table 2.

Steps in exosome absorption and associated factors.

Steps	Factors/Processes	Mechanisms	References
Exosome absorption
Exosome biodistribution and organ-specific accumulation	Retention in lymph nodes and bone	Exosome size	[14]
	Route of administration	Intratumoral, intravenous, etc.	[99,100,101]
	Cell type-specific rate of exosome uptake	Cell type-dependent factors	[102]
Targeting to recipient cell	Receptor–ligand interaction	RVG, SDF-1; integrins (αvβ5, α6β4, α6β1, α4β7), TSPNs (TSPAN8, CD63), CD47	[103,104,105] [112,113,114,115,116]
	Lipid targeting	Phosphatidylethanolamine, sphingomyelin	[106,107]
	Cell-type-specific exosome uptake	Recognition moieties from the donor cell type	[108,109,110,111]
Recipient cell interactions	Signal transduction via receptors	MHC-peptide complex, TNF receptors	[118,119]
	Membrane fusion	Rabs, SNARE; membrane rigidity and lipid content	[107,122]
	Clathrin-mediated endocytosis	Dynamin-2; transferrin	[117,124,125]
	Lipid raft endocytosis	Cholesterol, sphingolipid, flotillin	[126,127,128,129]
	Macropinocytosis	Rac1 GTPase, actin, cholesterol, EGFR	[130,131,132]
	Caveolin-dependent endocytosis	Caveolin-1	[133,134]
	Phagocytosis	PI3K, phosphatidylserine	[125,135,136,137,138]
Internalized exosomes	Lysosomal degradation	Trafficking to lysosomes (e.g., Rab7)	[80,139]
	Bypassing lysosomal degradation	Passive diffusion; cargo activation by acidification; RNA transfer to ER; fusion with endosomal membrane (e.g., LBPA)	[108,140,141,142,143]
	Re-release	Sorting to recycling endosomes	[144,145]

Abbreviations: RVG, rabies viral glycoprotein; TSPN, tetraspanin; ER, endoplasmic reticulum; LBPA, lysobisphosphatidic acid.