Table 2.
The application of exosomes-based exogenous miRNA delivery system in cancer treatment in the last decade
| Exosome | The source of exosome | Therapeutic cargo | Loading method | Target gene | Mechanisms | Cancer types (cell lines) | Effects | References |
|---|---|---|---|---|---|---|---|---|
| Engineering exosome (Apo-A1-modified exosome) | HEK293T cells | miR-26a | Electroporation | CCNE2, CDK6, CCND2 | Down regulating of the expression levels of CCNE2, CCND2 and CDK6 | Liver cancer (HepG2) | Decreasing the rates of cell migration and proliferation | [21] |
| Engineering exosome (GE11 peptide or EGF-modified exosome) | HEK293T cells | let-7a | HiPerFect transfection reagent | Unidentified or uncharacterized genes | Breast cancer (HCC70 HCC1954, MCF-7) | Inhibiting tumor development | [41] | |
| Engineering exosome (magnetic molecules and L17E peptide- modified exosome) | Serum | dox, cholesterol-modified miR-21 inhibitor | Co-incubation | miR-21 | Interfering with nuclear DNA activity and down regulating the expression of oncogenes bcl-2, caspase-3 and p-akt | Human glioblastoma (U87), breast cancer (MDA-MB-231) | Inhibiting the growth of the tumors and alleviating side effects | [108] |
| Stem-cell-derived exosome | Human umbilical cord mesenchymal stromal cells | miR-145-5p | Exo-Fect™ exosome transfection reagent | Smad3 | Activating the TGF-β/Smad3 pathways | Pancreatic ductal adenocarcinoma (Capan-1, CFPAC-1, BxPC-3, Panc-1) | Inhibiting cell proliferation and invasion and increasing apoptosis and cell cycle arrest | [109] |
| Stem-cell-derived exosome | Bone marrow mesenchymal stem cells | LNA-antimiR-142-3p | Electroporation | APC, P2X7R | Decreasing the levels of miR-142-3p and miR-150, and increasing the targeted regulation of APC and P2X7R | Breast cancer (MCF-7) | Reducing cell clonogenicity and tumorigenicity | [110] |
| Stem-cell-derived exosome | Human umbilical cord mesenchymal stem cells | miR-6785-5p mimic | Lipofectamine 2000 transfection reagent | INHBA | Inhibiting the expression of INHBA | Gastric cancer (SGC7901, MGC803) | Suppressing cell angiogenesis and metastasis | [111] |
| Stem-cell-derived exosome | Human bone marrow mesenchymal stem cells | miR-205 mimic | Lipofectamine 2000 transfection reagent | RHPN2 | Inhibiting the expression of RHPN2 | Prostate cancer (LNCaP) | inhibiting cell proliferation, invasion, and migration and promoting cell apoptosis | [112] |
| Stem-cell-derived exosome | Human umbilical cord mesenchymal stem cells | miR-139-5p mimic | Lipofectamine 2000 transfection reagent | PRC1 | Inhibiting the expression of PRC1 | Bladder cancer (T24, J82, UMUC3, 5637) | Impeding the cell proliferation, migration, and invasion potentials | [113] |
| cancer-associated fibroblasts | Cancer-associated fibroblasts | miR-3188 mimic | Lipofectamine 2000 transfection reagent | BCL2 | Downregulating the expression of BCL2 | Head and neck cancer (HN4, HN30) | Inhibiting cell proliferation, colony formation ability and G1 to S cell cycle transition | [114] |
| Cancer-associated fibroblasts | Cancer-associated fibroblasts | miR-320a mimic | Lipofectamine 2000 transfection reagent | PBX3 | Suppressing the activation of the MAPK pathway | Hepatocellular carcinoma (MHCC97-H, SMMC-7721, Huh7) | Suppressing cell proliferation, migration and metastasis | [115] |
| Cancer-associated fibroblasts | Cancer-associated fibroblasts | miR-139 mimic | Lipofectamine 2000 transfection reagent | MMP11 | Decreasing the expression of MMP11 | Gastric cancer (N87, AGS) | Inhibiting cell growth and metastasis | [116] |
| Cancer-associated fibroblasts | Cancer-associated fibroblasts | miR-34 mimic | Lipofectamine 3000 transfection reagent | AR, CCL22, CCND1, CCNE2, CDK4, CDK6, c-Met, E2F3, E2F5, HMGA2, LETK3, MTA2, N-Myc, PAR2, SFRS2, SIRT1 | Downregulating the expression of target genes | Gastric cancer (AGS, AZ521, MKN1, NUGC3) | Inhibiting cell proliferation and invasion | [117] |
| Exosome-liposome hybrid | Human ovarian cancer cells | miR497, triptolide | Liposome | PI3K, AKT, mTOR | activatingpi3k/AKT/mTOR signaling pathway | Ovarian cancer (SKOV3) | Signifcantly enhancing tumor cell apoptosis and overcoming chemoresistant ovarian cancer | [118] |
| Engineering exosome (Her2-LAMP2-modified exosome) | HEK293T cells | miR-21 inhibitor, 5-FU | Electroporation | miR-21 | Downregulating miR-21 and rescuing PTEN and hMSH2 expressions | Colon cancer (HCT-1165FR) | Reversing drug resistance and significantly enhancing the cytotoxicity in 5-FU-resistant colon cancer cells | [107] |
| HEK293T cells | Let7c-5p | Lipofectamine RNAiMAX reagent | HMGA2, c-Myc | Downregulating the expression of HMGA2 and c-Myc | Breast cancer (MDA-MB-231) | Inhibiting cell proliferation and migration | [119] | |
| Stem-cell-derived exosome | Bone marrow-derived mesenchymal stem cells | LNA anti-miR-142-3p | Electroporation | APC, P2X7R | Suppressing the expression level of miR-142-3p and miR-150 and increasing the transcription of the regulatory target genes, APC and P2X7R | Breast cancer (4T1) | Decreasing cell proliferation | [120] |
| Stem-cell-derived exosome | Human umbilical cord mesenchymal stem cells | miR-375 mimic | Transfection | ENAH | Suppressing ENAH expression | Esophageal squamous cell carcinoma (KYSE70, ECA109, EC9706) | Inhibiting cell proliferation, invasion, migration, tumorsphere formation, and promoting apoptosis | [121] |
| Engineering exosome (TAT peptide-modified exosome) | A549 cells | miR-449a | TAT-TAR interaction | Bcl-2 | Inhibiting the expression of apoptosis inhibitor protein Bcl-2 | Non-small cell lung cancer (A549) | Inhibiting cell proliferation and promoting cell apoptosis | [43] |
| Engineering exosome (T7 peptide-modified exosome) | HEK293T cells | miR-21 antisense oligonucleotides | Electroporation | miR-21 | Reducing of miR-21 and inducing the expression of PDCD4 and PTEN | Glioblastoma (C6) | Resulting in a reduction of tumor sizes | [106] |
| Cancer-cell-derived exosome | HT-29 and SW480 cells | miR-375-3p mimic | Modified calcium chloride method | ZEB1 | Reducing the expression of β-catenin, vimentin, ZEB1, and snail significantly increasing the expression of E- cadherin in EMT process | Colon cancer (HT-29, SW480) | Reversing EMT process and inhibiting cell invasion and migration | [44] |
| FHC cells | miR-128-3p mimic | Electroporation | Bmi1, MRP5 | Suppressing Bmi1 and MRP5 expression | Oxaliplatin-resistant colorectal cancer (HCT116OxR, HT29OxR) | Enhancing cell chemosensitivity | [122] | |
| HEK293T cells | miRNA-497 mimic | Transfection | YAP1, HDGF, CCNE1, VEGF-A | Suppressing YAP1, HDGF, CCNE1, VEGF-A expression | Non-small cell lung cancer (A549) | Inhibiting the tumor growth and angiogenesis | [123] | |
| SCC084 cisplatin- resistant strain | miR-30a mimic | Lipofectamine RNAiMAX | Beclin1 | A concomitant decrease in Beclin1 and Bcl2 expression | Oral squamous cell carcinoma (SCC084) | Regaining sensitivity of the cisplatin-resistant OSCC cells | [124] | |
| Cancer-cell-derived exosome | Oral cancer patients and oral squamous cell carcinoma (OSCC) | miR-155 mimic | Lipofectamine RNAimax | FOXO3a | Modulation of EMT pathway and downregulation of FOXO3a | Oral cancer (SCC131) | Conferring cisplatin resistance in OSCC | [104] |
| Parental and cisplatin-resistant human OSCC cell lines | miR-155 inhibitor | Modified calcium chloride transfection method | FOXO3a | Upregulation of FOXO3a and induction of the mesenchymal-to-epithelial transition | Oral squamous cell carcinoma (UPCI-SCC-131) | Reversing chemoresistance in oral cancer | [46] | |
| Cisplatin-resistant OSCC cells | Anti-miR-21 | Lipofectamine 3000 | PTEN, PDCD4 | Downregulating the expression of PTEN and PDCD4 | Oral squamous cell carcinoma (HSC-3, SCC-9) | Inducing cisplatin resistance of OSCC cells | [125] | |
| HEK293T cells | Anti-miR-214 | Lipofectamine 2000 transfection reagent | miR-214 | Downregulation of miR-214 and overexpression of possible target proteins (PARP9, XRCC, LIN28B) | Gastric cancer (SGC7901) | REVERSING chemoresistance and repressing tumor growth | [126] | |
| HEK293T cells | miR-199a-3p mimic | Lipofectamine 2000 transfection reagent | ZEB1, MTOR, DNMT3A | Down-regulation of underlying target proteins (ZEB1, MTOR, DNMT3A) | Hepatocellular carcinoma (Huh-7) | Reversing chemoresistance to cisplatin in hepatocellular carcinoma | [127] | |
| Doxorubicin-resistant gastric cancer SGC7901/ADR cell | miR-501 inhibitor | Lipofectamine 2000 transfection reagent | miR-501 | Inducing downregulation of BLID, inactivating of caspase-9/-3 and phosphorylation of Akt | Gastric cancer (SGC7901) | Being sensitive to doxorubicin and attenuating proliferation, migration and invasion and increasing apoptosis | [105] |