Table 1.
The use of extracellular vesicles (EVs) with or without modified cargo for antitumor therapy.
| Vesicle source | Vesicle type | Purification strategy | Cargo | Mechanism of action | Model | Reference |
|---|---|---|---|---|---|---|
| Cancer cells | ||||||
| Glioblastoma–astrocytoma U-87 MG cells | Exosomes | Exosome isolation reagent (Invitrogen) | DOX or PTX | Cell viability decrease | In vitro U-87 MG cell culture | (34) |
| LNCaP and PC-3 prostate cancer cells | Exosomes and microvesicles | Differential centrifugation | PTX | PTX cytotoxic effect increase | In vitro PC-3 and LNCaP cell culture | (33) |
| MDA-MB-231 and HCT-116 cell lines | Exosomes | ExoQuick-TC™ solution (System BioSciences) | DOX | Cardio toxicity decrease, DOX efficacy increase | MDA-MB-231 cell mice model in vivo | (35) |
| MDA-MB-231 and STOSE cell lines | Exosomes | AB cell culture-nanovesicles solution (AB ANALITICA) | DOX | Breast MDA-MB-231 and ovarian STOSE mouse tumors in vivo | (36) | |
| Oral cancer cells | Exosomes | Ultrafiltration and affinity chromatography | Tumor-associated antigens | NK cell proliferation and NK cell cytotoxicity increase | In vitro NK cell culture | (51) |
| Mouse malignant mesothelioma (MM) AB1 cells | Exosomes | Stepwise ultracentrifugation | Tumor-associated antigens | Exosome-loaded dendritic cell (DC) increased median and overall survival | AB1 tumor BALB/c mice model in vivo | (38) |
| Rat glioblastoma | Exosomes | ExoRNeasy Serum/Plasma Maxi Kit (Qiagen) | Tumor-associated antigens + α-galactosylceramide | Exosomes pulsed DCs increased median survival time | Glioblastoma-bearing rat model in vivo | (39) |
| UNKC6141 (pancreatic cancer) cells | Exosomes | Sucrose gradients ultracentrifugation | Tumor-associated antigens | Exosome-loaded DCs delayed tumor onset and increased survival time |
UNKC6141-bearing mice | (40) |
| DCs/Exo + all-transretinoic acid increased proliferation of lymph node cells and cytotoxic T cell activity | ||||||
| DCs/Exo and sunitinib prolonged survival time | ||||||
| DCs/Exo + gemcitabine prolonged survival time | ||||||
| Carcinoembryonic antigen (CEA)-expressing LS-174T tumor cells | Exosomes | Sucrose gradients ultracentrifugation | IL-18 | Maturation of DCs and induction of CEA-specific CD8+ CTL | DCs and CTL cells in vitro | (41) |
| OVA-expressing EL-4 lymphoma cells | Exosomes | Sucrose gradients ultracentrifugation | IL-2 | Immune response induction and tumor growth inhibition | C57BL/C mice model in vivo | (42) |
| YUSAC 2 melanoma cells | Exosomes | Sucrose gradients ultracentrifugation | Survivin-T34A (Survivin blocking protein) | Caspase activation and apoptosis induction | Pancreatic cancer cells in vitro | (43) |
| K562 leukemia cells | Exosomes | Differential centrifugation | TNF-related apoptosis-inducing ligand (TRAIL) | TRAIL-related apoptosis induction | SUDHL4 lymphoma and INT12 melanoma cells in vitro | (44) |
| Tumor growth inhibition | SUDHL4-bearing mice | |||||
| A549 cells | Exosomes | Differential centrifugation | Rab27a | Maturation of major histocompatibility complex (MHC) class II molecules, CD80 and CD86. Inhibition of tumor growth | DCs in vitro, BALB/c mice model in vivo | (47) |
| Glioblastoma multiforme (GBM) cells | Exosomes | Differential centrifugation | LRRC4 | Chemotaxis and expansion of CD4+ CCR4+ T cells | GBM cells in vitro | (45) |
| Hs578T and Hs578Ts(i)8 cells | Exosomes | Filtration and ultracentrifugation | miR-134 | Cellular migration and invasion reduction, drugs sensitivity enhancement | Hs578Ts(i)8 cells in vitro | (48) |
| SGC7901 cells | Microvesicles | Differential centrifugation | miR-29a and miR-29c | Angiogenesis and tumor growth suppression | Implanted with SGC7901 cells BALB/c mice in vivo | (49) |
| HeLa and HT1080 cells | Exosomes | Differential centrifugations and micro-filtration | Short interfering RNAs (siRNAs) against RAD51 and RAD52 | Accumulation of the cells in S and G2/M phases of cell cycle and recipient cell death induction | HeLa cells in vitro | (50) |
| Immune cells | ||||||
| DCs | Exosomes | Sucrose gradients ultracentrifugation | Lamp2b + iRGD + DOX | Tumor growth inhibition | MDA-MB-231 injected BALB/c nude mice model in vivo | (52) |
| DCs | Exosomes | Differential centrifugation | αGC + OVA | NK and γδ T-cell immune responses induction | Invariant NKT cells in vitro | (53) |
| Tumor growth decrease | B16/OVA melanoma tumor model in vivo | |||||
| DCs | Exosomes | Ultrafiltration/diafiltration and sucrose gradients ultracentrifugation | MHC class I and class II | NK cell proliferation and activation, IFNγ secretion enhancement | NK cells in vitro | (54) |
| MHC class I and class II | NK cell proliferation and activation by trans-presentation of IL-15 by IL-15Rα, number of metastases reduction | Mouse model in vivo | ||||
| DCs | Exosomes | Differential centrifugation | AFP | Survival rate prolongation | Tumor-bearing C57BL6 mice model in vivo | (55) |
| DCs | Exosomes | Ultrafiltration/diafiltration and sucrose gradients ultracentrifugation | IFN-γ | NKp30-dependent NK cell function enhancement | Advanced non-small cell lung cancer patients | (56) |
| RAW 264.7 macrophages | Exosomes | ExoQuick-TC™ solution (System BioSciences) | PTX | Drug cytotoxicity increase, inhibition of metastases growth | Resistant multidrug resistance cell culture in vitro, Lewis lung carcinoma mouse model in vivo | (57) |
| AA-PEG + PTX | Suppression of metastases growth and survival time increase | In vivo C57BL/6 mice lung cancer model | (58) | |||
| Monocytes or macrophages | Exosome-mimetic nanovesicles | Iodixanol gradients ultracentrifugation | DOX | Apoptosis increase and number of proliferating cells reduction | In vivo model of mouse CT26 colorectal cancer | (59) |
| Mesenchymal stem cells (MSCs) | ||||||
| MSCs | Exosomes | Differential centrifugation | Anti-miR-9 | Temozolomide sensitivity increase | Temozolomide-resistant GBM cell culture in vitro | (60) |
| MSCs | Exosomes | ExoQuick-TC™ solution (System BioSciences) | miR-146b | Tumor growth reduction | In vivo rat model of primary brain tumor | (61) |
| MSCs | Exosomes | Sucrose gradients ultracentrifugation | miR-124a | Viability and clonogenicity reduction | Glioma stem cell lines in vitro | (62) |
| Prolonged survival rate | In vivo model of mouse GSC267 glioma | |||||
| Bone marrow MSCs (BM-MSCs) | Exosomes | ExoQuick-TC™ solution (System BioSciences) | miR-340 | Tumor angiogenesis inhibition via the HGF/c-MET signaling pathway | Endothelial cell culture in vitro | (63) |
| MSCs | Exosomes | Differential centrifugation | Polo-like kinase 1 (PLK-1) siRNA | Cancer cell proliferation reduction by PLK-1 gene silencing | Bladder cancer cells in vitro | (64) |
| MSCs | Exosomes | ExoQuick-TC™ solution (System BioSciences) | miR-122 | Antitumor efficacy of sorafenib increase | Hepatocellular carcinoma model in vivo | (65) |
| BM-MSCs | Microvesicles | Differential centrifugation | PTX | Tumor growth inhibition | Human pancreatic adenocarcinoma CFPAC-1 cells in vitro | (66) |
| MSCs | Microvesicles | Differential centrifugation | PTX or GCB | Tumor proliferation inhibition | Pancreatic cancer cells in vitro | (67) |
| MSCs | Exosomes | Sequential ultracentrifugation combined with 0.22 µm ultrafiltration | TRAIL | Apoptosis induction | M231 breast cancer cells and other cancer cell lines in vitro | (68) |