Table 3. . Selected protein-based therapeutic cargos delivered via therapeutic extracellular vesicles.
| Delivered cargo | EV producer cell | EV target cell/tissue | EV delivery | Therapeutic application | Ref |
|---|---|---|---|---|---|
| Proteins | |||||
| 1. HSP60, HSP70, HSP90 | Hepatocarcinoma cell lines (HepG2; PLC/PRF/5) | K562, HepG2 cells | Cellular incubation | Cancer immunotherapy for induction of NK cell response | [27] |
| 2. Neprilysin endopeptidase (CD10) | Human adipose tissue-derived MSCs | N2a cells | Cellular incubation | Alzheimer’s disease therapy for degrading β-amyloid peptide (Aβ) | [28] |
| 3. Catalase | RAW A264.7 macrophage cells | PC12 neuronal cells, mouse brain | Cellular incubation and intranasal administration | Parkinson’s disease therapy across the BBB via oxidative stress reduction | [29] |
| 4. mCherry red fluorescent protein, Bax, IκB, Cre recombinase |
HEK293T embryonic kidney cells | HeLa cells, mouse brain | Cellular incubation and ventrolateral brain injection | Platform for efficient intracellular delivery of functional proteins | [30] |
| 5. Transferrin (Tf) & lactoferrin (Lf) iron carrier proteins |
THP1 monocyte cells | J774, CHO-TRVb, HepG2, THP1, spleen macrophages, etc | Cellular incubation | Platform for utilizing Tf and Lf for targeted intracellular delivery of therapeutics | [31] |
| 6. TRAIL surface membrane protein | MSCs | 11 different rTRAIL-sensitive or resistant cancer cell lines | Cellular incubation | Selective induction of apoptosis in cancer cells | [32] |
| 7. Saporin (ribosome-inactivating protein) | HeLa cells | CHO-K1 cells | Cellular incubation with electroporation | Platform for intracellular protein therapeutic delivery using cell-penetrating-peptide-modified exosomes | [33] |
| 8. RFP and GFP, luciferase | HEK293 cells | U87, HepG2, L929, iPS11, iPS15 cells | Cellular incubation | Platform for delivery of therapeutic membrane proteins via VSVG pseudotyping | [34] |
| 9. Ovalbumin | 293F cells | 293T, HeLa cells & C57BL/6J mice | Cellular incubation and mouse tail injections | Cancer immunotherapy for stimulation of CD4+ and CD8+ T cell response | [35] |
| 10. SIRPα (membrane protein) |
HEK293T cells | HT29 tumor cells | Cellular incubation | Cancer immunotherapy targeting of CD47 on tumor cells through delivery of SIRPα | [36] |
| 11. Cas9 | Vero and CHO cells | HuH7, HeLa cells | Cellular incubation | Intercellular delivery of functional CRISPR/Cas9 system | [37] |
BBB: Blood–brain barrier; EV: Extracellular vesicle; GFP: Green fluorescent protein; NK: Natural killer; RFP: Red fluorescent protein; SIRPα: Signal regulatory protein alpha; TRAIL: TNF-related apoptosis-inducing ligand; VSVG: Vesicular stomatitis virus glycoprotein.