Table 3.
EVs as drug delivery agents for cancer therapy.
| Therapeutic Agents | Cancer Type | Ev Source | Target Cell | Remarks | References |
|---|---|---|---|---|---|
| Small molecules | |||||
| Paclitaxel | Prostate | Prostate cancer cell lines, LNCaP and PC3 | Prostate cancer cell lines, LNCaP and PC3 | EVs isolated from the prostate cancer cells previously treated with Paclitaxel, increased the cytotoxicity of the drug in vitro against autologous prostate cancer cells. | [207] |
| Pancreatic | Murine SR4987 MSCs | Human pancreatic cell line, CFPAC-1 | EVs loaded with paclitaxel in vitro cancer cell proliferation. | [247] | |
| Doxorubicin | Lung | Human lung cancer cell lines, H1299 and YRC9 | Human lung cancer cell lines, H1299, A549, MRC9—lung fibroblast, HCASM—smooth muscle cells | Inhibited cancer cell growth in vitro. | [248] |
| Breast and ovarian | Human breast cancer cell line, MDA-MB-231, and mouse ovarian cancer cell line, STOSE | MDA-MB-231 and STOSE (used for In Vitro experiments and also injected into mice) | In vitro: presented cytotoxicity against cancer cells. In vitro: reduced tumor volume and cardiotoxicity compared with free doxorubicin. |
[249] | |
| Paclitaxel and doxorubicin | Brain | Brain endothelial cells, bEND.3 | Human brain neuronal glioblastoma—astrocytoma U-87MG xenograft in zebrafish | EVs delivered anticancer drug the blood-brain barrier to xenograft transplanted brain cancer cells. Reduced expression levels of VEGF RNAs compared with free drugs. |
[250] |
| Cisplatin | Lung | Tumor cells previously treated with chemotherapeutic drugs | Hepatocarcinoma cells—resistant murine H22, human breast cancer cell line, MCF-7, human lung cancer cell line, A549 | Extracellular vesicles released from tumor cells containing cisplatin reversed drug resistance and induced apoptosis in drug resistance tumor cells derived from patients with lung cancer. | [251] |
| AO | Melanoma | Macrophages | Melanoma cell line, Me30966 | Exosomes isolated form macrophages which contain AO increased apoptosis in melanoma cell line compared with free AO in vitro. | [252] |
| siRNAs | |||||
| VEGF siRNA | Brain | Brain endothelial cell line, bEND.3 | Human brain neuronal glioblastoma- astrocytoma U087MG xenograft in zebrafish | VEGF siRNA contained in exosomes crossed the blood-brain barrier to xenograft transplanted brain cancer cells to decrease tumor burden in vivo. | [253] |
| miRNAs | |||||
| Let-7 | Breast | Human breast cancer cell lines, HCC70, HCC1954 and MCF-7, expressing GE11 (a peptide which targets EGFR) | In Vitro—human cell line, HCC70. In Vitro—EGFR-expressing breast cancer xenograft tissue in Rag2-/- mice |
Exosomes which contain GE11 targeted EGFR that is expressed in cancer tissues and inhibited tumor growth compared with cancer tissue that contain non-let-7 and exosomes containing non-GE11 in vitro. | [216] |
| miR-122 | Liver | Human AMSCs | In Vitro—human liver cancer cell line, HepG2 In Vivo—injected mice with HepG2 cell line |
In vitro, exosomes that contain miR-122 in their structure induced apoptosis in liver cancer cell and decreased tumor growth in mice compared with exosomes which do not contain miR-122. | [217] |
| Anti-miRNAs | |||||
| Anti-miR-9 | Glioblastoma | Human mesenchymal stem cells | Human glioblastoma cell lines, U87 and T98G and glioma cell lines isolated from patient, BT145 and BT164 | In vitro, exosomes that contain anti-miR-9 reversed the resistance of glioblastoma cells to temozolomide compared with exosomes which does not contain anti-miR-9. | [243] |
| mRNAs | |||||
| CD-UPRT | Schwannoma | Human embryonic kidney cell line, HEK293T | In Vivo—HEI-193 cells in a Schwannoma orthotopic mouse model | In Schwannoma, mRNA of CD-UPRT-containing exosomes induced apoptosis and in vivo have the ability to reduced tumor growth via increasing 5-fluorocytosine sensitivity compared with the exosomes which does not contain CD-UPRT. | [254] |
| Proteins | |||||
| TRAIL | Myeloma | Human chronic myelogenous leukaemia cell line, K562 | In Vitro—human multiple myeloma cell lines, SUDHL, INT12 and KMS11 In Vivo—SUDHL and INT12 cells injected into mice |
In vitro: exosomes containing TRAIL have potential to induce myeloma cell death In vivo: reduced tumor growth in mice more efficient than free TRAIL |
[255] |
| hMUC1 | Colon | Mouse colon cancer cell line, CT26 and TA3HA, which expressed hMUC1 | MUC1-expresseing mouse cell lines in BALB/c nude mice In Vitro—BMDCs from BALB/c mice |
Exosomes that contain hMUC1 stimulated splenocytes through promoting IFNγ release In Vitro and In Vivo having the ability to suppress tumor growth compared with non-hMUC1 exosomes. | [256] |
EV: extracellular vesicle; MSCs: mesenchymal stem cells; VEGF: vascular endothelial growth factor; RNA: ribonucleic acid; mRNA: messenger RNA; siRNA: small interfering RNA; miRNA: microRNA; AO: Acridine Orange; EGFR: epidermal growth factor receptor; CD-UPRT: cytosine deaminase fused to uracil phosphoribosyl transferase; TRAIL: TNF-related apoptosis-inducing ligand; IFNγ: interferon gamma.