Table 2.

Multiple modified EVs encapsulate therapeutic cargo targeting various organs

Targeted organs	EV source	Modification	Therapeutic cargo	Injection method	Outcome	Refs.
Heart	CPCs	Transfection of miR-322 by electroporation after isolation of exosomes	miR-322	Tail intravenous injection	CPC-EV loaded with miR-322 can treat ischemic cardiovascular disease	[134]
	BMSC	Transfection of Lamp-2b with IMTP plasmid	Targeting peptide IMTP	Intravenous injections	IMTP-EVs are more easily taken up by hypoxia-injured cells, improving myocardial function	[108]
	CDCs	Transfection of Lamp-2b with CMP plasmid	Targeting peptide CMP	Intramyocardial injections and retroorbital intravenous injection	CMP-EVs improve selective targeting of ischemic heart tissue	[109]
	BMSCs(with hypoxic conditions)	Combine with IMT peptides through bio-orthogonal chemistry	miR-125b-5p	Intravenously injection	Improve the targeting efficiency of EV, reduce cardiomyocyte apoptosis and reduce off-target	[135]
	MSC	Platelet membranes to envelope EVs	–	Intravenous injections	Significantly increase the uptake of EVs by endothelial cells and cardiomyocytes, and reduce the phagocytosis of macrophages	[136]
Brain	MSC	Use click chemistry to couple functional ligands to the EV surface	Cur	Tail intravenous injection	cRGD-EV targets the ischemic brain injury area and inhibits inflammation and apoptosis in this area	[137]
	HEK 293 T cell line	Transfection of RVG peptide plasmid and mu (MOR) siRNA into donor cells	MOR siRNA	Intravenously injected	RVG EVs encapsulating MOR siRNA cross the BBB and target the central nervous system to treat drug addiction	[138]
	whole blood of SD rats	Coupling mAb GAP43 to the surface of Que-EV using the carbodiimide method	Quercetin	Tail intravenous injection	Que/mAb GAP43-EV enhances the accumulation of Que drugs at the site of cerebral ischemia injury and reduces the infarct size	[139]
	Neutrophil	–	Dox	Intracardiac injection; intravenously injected	NEs-EVs carries Dox across the BBB to target brain tumors	[140]
	Raw264.7	Combine RGE peptides with EVs loaded with SPION and Cur by click chemistry	SPIONs and Cur	Tail intravenous injection	RGE-EV-SPION/Cur can cross the blood–brain barrier, accurately identify and treat gliomas	[110]
Lung	BMM	Combine the mixture of EVs and DSPE-PEG-AA using ultrasound and PTX	PTX	Tail intravenous injection	AA-PEG-EV specifically delivers PTX to lung metastases	[141]
Bone	Dendritic cells	CAP-EV was synthesized by transfection of CAP-lamp2b plasmid	miR-140	Intraarticular injection	CAP-EVs remain in the joint cavity, deliver miR-140 to deep cartilage regions, and alleviate OA progression	[25]
	Endothelial cells	–	miR-155	Intraperitoneally injection	EC-EV is specifically taken up by BMMs, among which miR-155 inhibits osteoclast activity and reverses osteoporosis	[80]
	NIH-3T3 cells	Plasmid transfection enables high expression of CXCR4 on the surface of EVs	Antagomir-188	Tail intravenous injection	CXCR4-positive EVs could be recruited to the bone marrow	[79]
Skin	Human adipose tissue-derived mesenchymal stem cell	–	–	Intravenously or subcutaneously	Topical application	[142]
Liver	MSC	The EVs modified with cationized pullulan	–	Tail intravenous injection	The modified EVs accumulated in the liver tissue, resulting in a greater therapeutic effect on liver injury	[128]
Breast	imDCs	Transfect iRGD peptide binds to the exosomal surface membrane protein Lamp-2b	Dox	–	iRGD-EVs-Dox can be specifically delivered to the breast, playing a highly effective anti-tumor effect	[143]
Colon	Raw264.7	Produce HDEA@EVs including PH response HDEA, hyaluronic acid and Dox	Dox	Tail intravenous injection	HDEA@EVs specifically binds to the CD44 receptor on the tumor surface and delivers Dox to colon cancer tumor cells	[144]

CPCs, Cardiac progenitor cells; BMSC, Bone Marrow Stromal Cells; IMTP, Ischemic myocardium-targeting peptide; CDCs, Cardiosphere-derived cells; CMP, Cardiomyocyte specific peptide; MSC, Marrow Stromal Cells; RGD, L-Asparticacid,L-arginylglycyl-; Cur, Curcuminoid; RVG, Rabies viral glycoprotein; HEK293, Human embryonic kidney 293; MOR, Opioid receptor Mu; BBB, Blood–brain barrier; SD rat, Sprague–dawley rat; GAP43, Growth-associated protein-43; Que, Quercetin; Raw264.7, Leukemia cells in mouse macrophage; Dox, doxorubicin; NE, Neutrophil; SPIONs, Superparamagnetic iron oxide nanoparticles; RGE, Neuropilin-1-targeted peptide; BMM, Bone-marrow derived macrophages; PTX, Paclitaxel; AA-PEG, Aminoethylanisamide-polyethylene glycol; CAP, Chondrocyte-affinity peptide; OA, Osteoarthritis; EC, Endothelial cells; CXCR4, C-X-C motif chemokine receptor 4; imDC, immature dendritic cells; HDEA, Hyaluronic acid grafted with 3-(diethylamino)propylamine