fig2

Figure 2. Reengineering PELNVs as nanoscale therapeutics. (1) Using lipophilic or amphiphilic molecules, these molecules can be directly inserted into the EV membrane through the hydrophobic interaction with the phospholipid bilayer. (2) Enzyme catalytic reaction, for example, sortase enzyme can react the sequence of LPETX with the N-terminal protein on exosomes. (3) Metabolic labeling, in which metabolite analogs are incorporated into cell biosynthesis, and functional groups (such as azide) can be introduced into EVs, thereby allowing subsequent bio-orthogonal reactions. (4) Chemical reactions can also be carried out directly on the vesicle membrane. For example, carbodiimide can modify natural amines to present azide groups for click chemistry reactions. (5) Exogenous substances can be introduced through liposomes or micelles fused with the exosomal membrane. (6) Genetic engineering can be used to fuse coding genes on exosomal membrane proteins.