Table 3.

Differences between small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs)

Characteristic	sEVs	lEVs	References
Size	The mean size is approximately 79 nm Typically, it ranges in diameter from 30 to 150 nm	Start at a size of 100 nm and can be much larger	[110, 111]
Isolation method	Higher centrifugal forces compared to lEVs	Differential centrifugation	[110, 111]
Cargo	They transport proteins, mRNA, miRNAs, and lipids, which can modulate the tumor microenvironment, promote immune suppression, and facilitate metastasis	They are enriched with chromosomal DNA, including large fragments of up to 2 million base pairs. This DNA content reflects the genomic alterations of the tumor of origin, making lEVs a valuable source for detecting tumor-derived genomic changes	[112–115]
Protein content	sEVs are enriched in proteins associated with cell adhesion and signaling pathways, contributing to their role in promoting cellular adhesion and motility	lEVs are enriched in proteins associated with ribosomes and RNA biogenesis, suggesting various functional roles	[116]
Roles in cancer	sEVs are involved in cancer progression by delivering bioactive cargos that reprogram target cells, promoting tumor growth, invasion, and metastasis. They are also being explored as drug carriers and anti-cancer vaccines due to their ability to modulate immune responses and create pre-metastatic niches	lEVs carry most of the tumor DNA circulating in the plasma of cancer patients, such as those with prostate cancer. This makes them a critical component for studying tumor-derived genomic alterations and potentially guiding personalized cancer therapies	[112, 114, 115, 117]