Fig. 4

Different modification strategies for improving EV targeting. A Indirect modification. Overexpressed targeting molecules in parental cells fused to EV-enriched fusion partner proteins by vesiculation to obtain EV targeting. B Chemical modification. a. Click chemistry. Through azide–alkyne cycloaddition, different biomolecules are covalently bound to EV surfaces that endow them with specific functionality. b. Lipid/hydrophilic insertion. Lipids or hydrophilic molecules can be inserted into the lipid bilayer of EVs and were displayed on the EV surfaces. c. Multivalent electrostatic interactions. Change the membrane potential by binding to cations. d. CP05 peptide anchor. Based on the high affinity of CP05 peptide for CD63 molecule, the targeting moiety was loaded on the EV surface. e. Direct fusion. With the help of lipophilic nature, markers (such as DiR/DiO, 111In-oxine) are directly fused with the lipid bilayer of EVs. C Physical modification. Under the guidance of MF, EVs can be magnetically navigated to target sites