Table 1.

The exosome-based drug-carrying method

	Method	Mechanism	Merits	Demerits
Active	Sonication	Additional mechanical shear forces weaken the integrity of the outer body membrane with ultrasound[44]	High loading efficiency	Disruption of exosome integrity;Causes exocrine remodeling/deformation
	Surfactant treatment (e.g., Saponin)	Co-cultured with saponin solutions and then purified by dialysis membranes and chromatographic columns	Directly Incorporation of proteins; High loading efficiency	Hemolytic activity
	Extrusion	Mixing of target drugs with crushed exosome membranes using an extruder with nanoporous membranes[45]	High loading efficiency; uniform particle size	Possible changes of the exosome membrane and the zeta potential of the original exosomes
	Freeze-thaw cycles	Repeatedly frozen at -80°C or lower (liquid nitrogen), then thawed at room temperature[46]	High loading efficiency; Simple	Aggregation of exosomes
	Electroporation	Short high voltage electrical pulses form micropores in the exosome membrane	Loading with large molecules and smaller hydrophilic molecules	the risks of RNA and exosomes aggregation
	Chemical transfection	Gene edition[47]	Stability; high loading efficiency for peptides, proteins, and nucleic acids	Time and financial consumption; hard to quantitation; poor controllability
Unactive	Direct ncubation of drugs with exosomes	Different drug concentration gradients	Simple	Low loading efficiency
	Mixing with exosome donor cells after co-incubation	Cells cytosolicize the drug and then secrete it exosomes loaded with drugs	Simple	Low oading efficiency and low output drug concentration
Targeted delivery methods	Engineered exosomes	Genetic engineering modification of extracellular surface proteins[43]	Convenient, simple, and targeted	Possible changes to the protein alteration