Table 1.

Modification strategies of exosomes for applications in contrast media and radionuclide composition as well as theranostic development.

Exosome Modification Technique	Advantages	Disadvantages
Direct incubation	The simplest approach for loading functional molecules into the cavities of exosomes	Low loading efficiency, lack of selectivity
Electroporation	Stimulation of external electric fields and production of nano-sized pores on the surface through which functional molecules can enter into the inner spaces	Loading of hydrophobic agents may be inefficient
Sonication	The shear force generates nano-sized pores on the surface of the membrane letting the molecules diffuse into the cavity	The recovery of the membrane after sonication took approximately one hour and is required to reduce the leakage of the packaged molecules
Phospholipid substitution	Dynamic exchange of the phospholipid between the cells and the phospholipid derivate within the culture medium	Phospholipid derivate could only target tumor cells expressing the folate receptor
Covalent coupling	Functionalisation of exosomes with antibodies and other functional molecules by chemical coupling	Surface constitution of exosomes is too complicated, and the surfaces lack relevant active functional groups which are necessary for covalent coupling
Aptamer technique	Direct and selective engineering of the surface of exosomes with functional DNA	Unstable delivery of these membrane molecules to the shedding EVs
Gene engineering	Giving exosomes different functions as they are directly shed from the membranes of the engineered maternal cells	Poor expression of these membrane molecules to the shedding EVs