Table 3.
Representative examples of EVs used as therapeutic agent carriers.
| Application | Therapeutic agent | Donor cell | Loading strategy | Advantage | Ref. |
|---|---|---|---|---|---|
| Cancer therapy | PTX | Cow milk | Incubation | Exhibiting low systemic toxicity and excellent stability | 98 |
| 5-FU, miR-21i and Her2 affibody-LAMP2-EGFP | Colorectal cancer (HCT-1165FR) | Electroporation | Targeting cancer cells overexpressing Her2; Facilitating cellular uptake and improving the cytotoxicity for 5-FU-resistant cells | 99 | |
| AFP antigen | Dendritic cells | Lentivirus | Disseminating antigenic material among DCs | 105 | |
| Tumor specific antigen and CpG DNA adjuvant | Melanoma (B16) | Incubation | Delivering CpG-EVs tumor specific antigen; Exerting stronger anti-tumor effects than co-delivery | 107 | |
| BFGF antigen | E. coli | Transfecion (plasmid) | Producing persistent anti-BFGF auto-antibodies | 110 | |
| DOX | Glioblastoma (bEnd.3) | Sonication | Crossing the BBB; Escaping lysosomal degradation; Low cytotoxicity and exhibiting excellent tumor suppression effect | 175 | |
| Infectious disease vaccine | Adjuvant | B. pseudomallei (strain Bp82) | – | Low toxicity and strong immunostimulation | 2 |
| The specific antigen peptide | B. pertussis (strain B1917) | – | Eliciting high antibody level and inducing broad humoral response | 122,123 | |
| Lipid IVa instead of full LPS | E. coli | Transduction (phage) | Serving as the adjuvant to show high immunogenicity and low toxicity | 125 | |
| dPNAG polysaccharide antigen | E. coli (strain BL21) | – | Broadly eliminating pathogens expressing PNAG on the surface | 129 | |
| PorA N. meningitidis antigen | N. meningitidis (strain PL16215 or PL10124) | – | Evoking strong humoral immune response and produce a powerful protective effect | 131 | |
| Regenerative medicine | Proteins and nucleic acids with repaired and regenerative functions | Mesenchymal Stem cells (main) | – | Enhance lung tissue regeneration in multiple pathways | 150 |
| Proteins and nucleic acids with repaired and regenerative Functions, fibrinogen and thrombin | Mesenchymal stem cells | Co-delivery | Extending the retention and promote uptake of EVs | 151 | |
| Proteins and nucleic acids with repaired and regenerative functions, fibrous polyester materials | Mesenchymal stem cells | Incubation | Prolong the retention of EVs; Recruit and active uptake EVs of immune cells | 151 | |
| Gene therapy | CRISPR/Cas9 | Ovarian cancer (SKOV3) IVA | Electroporation (CRISPR/Cas9-expressing plasmid) | Achieving to load large molecule nucleic acids; CRISPR/Cas9 selectively accumulate in cancer cell | 157 |
| CRISPR/Cas9 | 293T | Incubation (EVs fuse with liposome carrying CRISPR/Cas9-expressing plasmid) | Higher loading efficiency than electroporation | 158 | |
| CRISPR/Cas9 | 293T | Transfection (CD9-HuR (plasmid) and sgRNA-Cas9 (lentivirus)) | Improving gene editing efficiency, safety and flexibility | 160 | |
| CRISPR/Cas9 | 293T | Transfection (GFP-CD63 (plasmid) and sgRNA-Cas9-GFP Ab (plasmid) | Improving gene editing efficiency, safety and flexibility | 161 | |
| CRISPR/Cas9 | 293T | Transfection (com-sgRNA (plasmid), Com-CD63-Com (plasmid) and Cas9-com (plasmid)) | Improving gene editing efficiency, safety and flexibility | 162 | |
| miR-31 | 293T | Transfection (lentivirus) | Promoting the wound healing; safety | 164 | |
| miRNA (Let-7i, miR-142 and miR-155) | Breast cancer (41T) | Electroporation | Modulating immune response and tumor microenvironment to reduce tumor burden | 165 | |
| Neuron-specific RVG peptide and miRNA | Not available | Electroporation | Crossing BBB, target specific cells | 166 | |
| siRNA | Pancreatic cancer (PANC-1) | Electroporation | Lower toxicity and equal treatment efficiency comparing with transfection reagent | 169 | |
| Low-density lipoprotein receptor (Ldlr) mRNA | Liver cell (AML12) | Transfection (plasmid) | Mainly targeting the liver then producing ample Ldlr protein | 170 | |
| DNA | Not available | Sonication or saponin | High loading efficiency | 171 | |
| Linear DNA | 293T or HUVEC | Electroporation | Every large size EV contains hundreds of DNA | 172 |