Table 2.

Application Examples of Surface Modification

Surface Modification Methods	Targeting Method	Drug Loading	Targeted Tissues and Applications	Ref.
Genetic Engineering	Dendritic cells (DCs) are genetically modified to express fusion proteins containing the membrane protein Lamp2b and RVG peptides, and engineered exosomes are harvested from the cells.	siRNA (Electroporation)	Targeting the central nervous system (neurons, microglia, oligodendrocytes) to treat Alzheimer’s disease	[126]
Chemical reaction combined with post-insertion	c (RGDyK) is a tumor-targeting peptide. DSPE-PEG 2000-cRGDyK is prepared by chemical reaction. The ligand is spontaneously inserted into the exosomal lipid bilayer through hydrophobic interactions and combined to obtain the targeted exosomes.	PTX (Co-incubation)	It can penetrate the blood-brain barrier, target glioblastomas, and significantly reduce the activity of cancer cells.	[135]
Genetic Engineering	Donor cells are engineered to express the transmembrane domain of the platelet-derived growth factor receptor fused to the GE11 peptide to achieve targeting, thereby assimilating exosomes from this source.	let-7a miRNA (Transfection)	Targeting breast cancer tissues expressing EGFR to treat breast cancer	[136]
Genetic Engineering	Engineered mouse immature dendritic cells expressing Lamp2b fused to iRGD peptide to produce tumor-targeted exosomes.	DOX (Electroporation)	It targets tumor tissues, inhibits the growth of tumor, and has good antitumor activity.	[119]
Chemical reaction	Extracellular vesicles containing azide lipids were firstly prepared and then conjugated to the targeted peptide using a copper-free catalytic click chemistry.	PTX, TPZ (Loaded on liposomes)	Targeting tumor cells	[101]
Electrostatic interaction	The complex formed by a cationic lipid and a pH-sensitive fusion peptide binds exosomes through electrostatic interaction to target the receptor cell membrane.	Dextran, Saponin (Electroporation)	Targeting the receptor’s cell membrane to enhance cell uptake and cytoplasmic release of exosomes	[137]
Magnetic nanoparticle technology	The SPMN-Tf conjugates were co-incubated with pre-dialyzed serum to form SMNC-Exo through interaction with the Tf-Tf receptor. After drug loading, SMNC-Exos were concentrated in the tumor region in the presence of an external magnetic field.	DOX (Co-incubation)	Targeting mouse subcutaneous H22 cells to inhibit the growth of tumor	[138]