TABLE 1.
EV surface modification for heart targeting.
| Surface modification strategy | Surface modification method | EV source | Targeting peptide | Animal model | Treatment outcome | References |
| Biological | Fused the CTP peptide to the Lamp2b protein by introducing a plasmid into HEK 293 cells | HEK 293 cells | APWHLSSQYS RT |
MI mice | The delivery of EVs to the hearts was increased by 15% than control in vivo and 16% in vitro | (83) |
| Biological | Molecular cloning and lentivirus packaging to engineer Lamp2b fused with CTP peptide | BMSCs | CSTSMLKAC | MI mice | Modificated EVs were increasingly accumulated in the ischemic heart area | (82) |
| Biological | Engineered CDCs to express Lamp2b, which was fused to a CTP peptide by Lentivirus | Cardiosphere-derived cells | WLSEAGPVV TVRALRG TGSW |
MI mice | Improved EVs uptake by cardiomyocytes in vitro and in vivo, decreased cardiomyocyte apoptosis | (84) |
| Chemical | Conjugated Exo with CTP peptide by bio-orthogonal chemistry | BMSCs | CSTSMLKAC | MI mice | Modificated EVs showed specific targeting to the ischemic lesions in the injured heart | (78) |
| Chemical | Conjugated EVs with CTP peptide through a DOPE-NHS linker | Cardiosphere-derived stem cells | CSTSMLKAC | MI rat | Increased retention of the EVs within heart sections ex vivo and in vitro | (79) |
| Chemical | Embed EV surfaces with an anchor conjugated to streptavidin | Cardiosphere derived cells | CSTSMLKAC | MI rat | Enhanced uptake in cardiac fibroblasts, myoblasts and ischemic myocardium | (80) |
| Chemical | Conjugated EVs with CTP peptide through a DOPE-NHS linker | human plasma EV | CSTSMLKAC | MI mice and dog | Improved cardiac retention of EVs in mice and dogs | (81) |
| Physical | Mixed EVs and platelet membrane and extruded them through filters | MSCs | N/A | MI mice | The uptake rate of platelet-membrane-hybrid exosomes that is 2–3 folds higher than that of control exosomes by endothelial cells, and 5–8 folds higher by cardiomyocytes | (85) |
| Physical | Mixed monocyte membrane vesicles and EVs and extruded with polycarbonate membrane | BMSCs | N/A | MI mice | Exhibited a high targeting efficiency for injured myocardium and improved therapeutic outcomes in cardiac function | (86) |
EVs, extracellular vesicles; CTP, cell targeting peptide; BMSCs, bone marrow mesenchymal stem cells; MSCs, mesenchymal stem cells; MI, myocardial infarction.