Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine
Abstract
:1. Introduction
2. EVs’ Post Isolation Direct Engineering
2.1. Chemico-Physical Functionalization
2.2. Loading Nanotechnological Modification into EVs
3. EVs’ Indirect Nanotechnological Modification through Parent Cells’ Engineering
3.1. Indirect Surface Functionalization
3.2. Indirect Loading
4. Conclusions and Future Outlook
Author Contributions
Funding
Conflicts of Interest
References
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EVs Type | Nanotechnological Modification | Application | Reference |
---|---|---|---|
Exosomes from 4T1, MCF-7 and PC3 cells | Labeling with DiR a | In vivo fluorescence imaging of tumor-derived exosomes | [47] |
Exosomes from 4T1 cells | Surface conjugation with azide-fluor545 by click chemistry | In vitro fluorescence imaging | [50] |
Exosomes from PC12 cells | Labeling of exosomes proteins with TAMRA-NHS b | In vitro fluorescence imaging | [49] |
Exosomes from fetal bovine serum | PEGylation by post-insertion of DSPE-PEG-mannose or chemical conjugation of NHS-PEG | Stealth and targeted Exosomes for elevated uptake in DCs | [54] |
Exosomes from embryonic stem cells | DSPE-PEG-c(RGDyK) | Targeting glioblastoma, lung cancer and prostate cancer cells | [73] |
Exosomes from RAW 264.7 cells | Post-insertion of DSPE-PEG-AA | Stealth and targeted exosomes for the in vitro and in vivo treatment of lung cancer | [55] |
EVs from Neuro2A cells | Post-insertion of DMPE-PEG-EGa1 nanobody | Stealth and targeted EVs for the in vitro and in vivo treatment of cancer cells | [52] |
EVs from HEK 293T cells | Post-insertion of cholesterolTEG-pRNA3WJ-targeting ligands | Targeted EVs for the in vivo treatment of breast, prostate and colorectal cancer | [57] |
Exosomes from MSCs | Chemical functionalization with cationized pullulan | Targeted exosomes for the in vitro and in vivo treatment of liver injury | [74] |
EVs from MLP29 cells | Modification of EVs surface glycosylation by neuraminidase | Modification of EVs glycosylation for altered in vivo biodistribution | [67] |
EVs from U87 and GBM8 cells | Enzymatic modification of EVs surface glycosylation and insertion of targeting ligand to DC-SIGN | Modification of EVs glycosylation and insertion of targeting ligand for improved uptake in DCs | [68] |
Exosomes from Hela cells | Hexadecaarginine (R16) peptide, an arginine-rich cell-penetrating peptide | Activation of the macropinocytosis pathway, affecting cellular uptake of EVs | [75] |
Exosomes from HeLa cells | Modification with LTX and GALA peptide via electrostatic interactions | Charge modified exosomes for enhanced cellular uptake and in vitro cytosolic release | [59] |
Exosomes from transfected HEK 293T | Glycosylation of targeting-peptide-Lamp2b fusion proteins | Stabilization of targeting peptide-Lamp2b fusion protein with glycosylation motif | [70] |
Exosomes from human colorectal carcinoma | Fe3O4 Superparamagnetic nanoparticles with high density A33 antibody | Antiproliferative effect in colorectal cancer | [71] |
Extracellular vesicles from fibroblasts | Apoptotic peptide Lys-Leu-Ala (KLA) or LDL | Extravasation across BBB and target glioblastoma multiforme | [72] |
Exosomes from bovine milk | Folic acid | Human lung and breast cancer reduction | [41] |
Plasma membrane vesicles | Bond of the EGF ligand to the transmembrane domain of transferrin receptor | Target EGFR-expressing cancers | [76] |
Exosomes-like nanoparticles from grapefruit | Inflammatory related receptor enriched membranes of activated leukocytes | Target inflammatory tumor tissues | [77] |
EVs Type | Nanotechnological Modification | Application | Loading Method | Reference |
---|---|---|---|---|
Exosomes from mesenchymal stem cells | Glucose-coated gold nanoparticles (NPs) | In vivo neuroimaging | Co-incubation | [78] |
Exosome from lung cancer or fibroblasts | Gold NPs and doxorubicin | Lung cancer treatment | Co-incubation | [118] |
EVs from breast adenocarcinoma | MOF NPs. NPs matrix contained gelonin | Inhibit adenocarcinoma growth | Sonication and extrusion | [119] |
Exosomes from Hela cells | MOF NPs | Hela cells | Co-incubation | [82] |
EVs from KB cells | ZnO NPs | Cytotoxic effect against KB cells | Co-incubation | [122] |
EVs from endothelial, cancer and stem cell lines | Porphyrins | To improve photodynamic therapy | Electroporation, extrusion, saponin-assisted and dialysis | [97] |
Exosomes from embryonic stem cells | Paclitaxel | Glioma therapy | Co-incubation | [73] |
Milk-derived exosomes | To reduce paclitaxel’s side effects | Co-incubation | [102] | |
Exosomes from macrophages | To overcome MDR in cancer cells | Co-incubation, electroporation and sonication | [56] | |
Exosomes from brain cell lines | To treat brain tumor | Co-incubation | [81] | |
EVs from prostatic cancer | Cytotoxic effect against prostate cancer | Co-incubation | [83] | |
Exosomes from human colorectal carcinoma | Doxorubicin | Antiproliferative effect in colorectal cancer | Dialysis | [71] |
Exosomes from breast cancer | To treat breast and ovarian cancer | Electroporation | [106] | |
Exosomes from breast cancer | To reduce cardiotoxicity of doxorubicin | Electroporation | [107] | |
Exosomes from 4T1, MCF-7, and PC3 cell line | Breast cancer | Co-incubation | [47] | |
Exosomes from mouse immature dendritic cells | For targeted delivery of chemotherapeutic | Electroporation | [79] | |
Milk-derived exosomes | Curcumin | Cervical cancer | Co-incubation | [109] |
Exosomes from lymphoma cells | Activate myeloid cells in vivo | Co-incubation | [123] | |
Plant exosomes | Colon cancer | NCT01294072 | ||
Milk-derived exosomes | Paclitaxel, Docetaxel, Withaferin A and curcumin | Targeting and therapy of lung cancer cells | Co-incubation | [41] |
Milk-derived exosomes | Celastrol | Inhibition of Hsp90 and NF-κB a activation pathways in lung cancer | Co-incubation | [124] |
EVs from lung cancer | Oncolytic adenovirus and paclitaxel | Enhance immunogenicity in lung cancer | Co-incubation | [125] |
Exosomes from HEK 293 cells | siRNA | Efficient delivery of siRNA in cancer cells | Electroporation | [126] |
Exosomes from HEK 293 cells | Polo-like kinase 1 (PLK-1) siRNA | Silencing PLK-1 gene in bladder cancer cells | Electroporation | [127] |
Exosomes from HEK 293 and MCF-7 cells | siRNA, miRNA and ssDNA b | Oncogene knockdown | Sonication | [95] |
Plasma-derived EVs | miRNA cel-39 | Promote apoptosis of hepatocellular carcinoma | Electroporation | [128] |
EVs Type | Nanotechnological Modification | Application | Reference |
---|---|---|---|
Exosomes from breast cancer | Ac4ManNAz labeled with ADIBO-fluorescent dyes | Breast cancer imaging | [133] |
Exosomes from melanoma | Gaussian Luciferase | Biodistribution and tumor targeting | [137] |
Exosomes from HEK 293T | [134,135] | ||
Exosomes from melanoma | [136] | ||
Exosomes from HEK 293T | Alexa Fluor 680-Streptavidin | Biodistribution and tumor targeting | [135] |
Exosomes from different cell lines | GFP | Monitoring and tracking of exosomes uptake in different types of cancer | [130,131,132,149] |
EVs from HEK 293T | Palmitoylation signal genetically fused in-frame to the N terminus of enhanced green fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) | Monitoring the uptake by cancer cells | [150] |
Exosomes from macrophage | Arginyl–glycyl–aspartic acid (RGD)-functionalized DSPE-PEG (DSPE-PEG-RGD), sulfhydryl-functionalized DSPE-PEG (DSPE-PEG-SH) and folic acid | Targeting Hela cells | [148] |
EVs from squamous cell carcinoma | DSPE-PEG-Biotin and folate | Targeting breast cancer for diagnosis and therapy | [145] |
Exosomes from HUVEC | DSPE-PEG-biotin | Targeting hepatocellular carcinoma | [147] |
EVs from macrophage | DSPE-PEG-Biotin and folate | Targeting Hela cells | [86] |
EVs from HUVEC | DSPE-PEG-Biotin | Targeting melanoma | [146] |
Exosomes from HEK 293T | DARPins | Targeting HER-2 over-expressing cancer cells (breast, ovarian and gastric cancers) | [139] |
Exosomes from HEK 293 | Anti-HER2 scFv antibody (ML39) | Inhibit the growth of HER2 positive breast cancer | [140] |
Exosomes from murine melanoma | Streptavidin-lactadherin fusion protein linked with biotinylated pH-sensitive fusogenic GALA peptide | Cancer immunotherapy | [138] |
Extracellular vesicles from murine neural stem cells | Anti-EGFR fused to GPI anchor signal peptides | Targeting of Hela cells | [143] |
Exosomes from dendritic cells | Lamp2b fused with iRGD (CRGDKGPDC) targeting peptide for αv integrin | Targeting breast cancer | [79] |
Exosomes from dendritic cells | Carcinoembryonic antigen or HER2 linked to the C1C2 domain of lactadherin | Targeting breast cancer | [141] |
Exosomes from HEK 293F cells | Prostate-specific antigen, and prostatic acid phosphatase linked to the C1C2 domain of lactadherin | Targeting prostate cancer | [142] |
Exosomes from fibrosarcoma cells | Chicken egg ovalbumin by fusing it to the C1C2 domain of the lactadherin | In vivo fibrosarcoma. More efficient antitumor immune response | [151,152] |
Exosomes from dendritic cell line | C1C2 domain of lactadherin is fused to soluble proteins or extracellular domain of membrane proteins | Generate antibodies against tumor biomarkers | [153] |
Transmembrane protein HLA-A2 a |
EVs Type | Nanotechnological Modification | Application | Reference |
---|---|---|---|
Human placental mesenchymal stem cells | Hollow gold NPs | Hyperthermia therapy against different type of cancer | [181] |
Exosomes from hepatocellular carcinoma | Porous silicon NPs loaded with doxorubicin | Decreased the expression of multidrug-resistant protein P-glycoprotein | [182] |
EVs from mesenchymal stem cells | SPIONs | Therapy against leukemia | [183] |
EVs from HUVEC | Iron oxide NPs and clinical photosensitizer (Foscan) | Phototoxicity against prostate adenocarcinoma cells | [120] |
Extracellular vesicles from human macrophages | Iron oxide nanoparticles and m-THPC photosensitizer | Theranostic approach against cervical and prostate cancer | [177] |
Microvesicles from different cancer cell lines | A hydrophobic photosensitizer zinc phthalocyanine encapsulated in liposomes | Photodynamic therapy for different cancer cell lines | [179] |
Microvesicles from human macrophages | Doxorubicin, tissue-plasminogen activator and two photosensitizers | Targeting and therapy of ovarian and prostate cancers | [178] |
Exosomes from mesenchyme stromal cells | Paclitaxel | Treatment of pancreatic cancer | [101] |
Exosomes from melanoma cell line | Survivin-T34A and Gemcitabine | Treatment of pancreatic adenocarcinoma | [175] |
Apoptotic bodies from tumoral cells | Doxorubicin or Metotrexate | Tumor cells killing with reduce side effects | [176] NCT01854866 |
Exosomes from breast cancer | Curcumin | Reverse inhibition of NK cell tumor cytotoxicity in breast cancer | [110] |
Exosomes from HEK 293 | P53 gene | Transfer p53 gene to p53-deficient cells | [184] |
Exosomes from HEK 293T | miR-21 sponges | Therapy for leukemia cells | [174] |
Extracellular vesicles from breast cancer | Anti-miR-21 | Theranostic method for breast cancer | [121] |
Exosomes from HEK 293T | Inhibitor of miR-214 | Reverse chemoresistance to cisplatin in gastric cancer | [165] |
Exosomes from prostate cancer cells | Anti-miR-21 spherical nucleic acid | Prostate cancer | [155] |
Exosomes from mammary carcinomas | miR-134 | Increase sensitivity of breast cancers to chemotherapeutic drugs | [166] |
Exosomes from mesenchyme stem cells | miR-122 | Increase sensitivity of hepatocellular carcinoma to chemotherapeutic drugs | [167] |
Exosomes from mesenchymal stem cells | miR-143 | Inhibit migration of osteosarcoma cells | [169] |
Exosomes from mesenchymal stem cells | anti-miR-9 | Increase sensitivity of glioblastoma multiforme to chemotherapeutic drugs | [170] |
Exosomes from mesenchyme stem cells | miR-146b | Inhibit glioma growth | [168] |
Microvesicles from HEK 293T | Suicide gene mRNA and protein-cytosine deaminase fused to uracil phosphoribosyltransferase | Inhibit schwannoma tumor growth | [171] |
Exosomes from HEK 293T | HGF siRNA | Inhibition of tumor growth and angiogenesis in gastric cancer | [172] |
Exosomes from breast cancer cells | RAD51 and RAD52 siRNA | Gene therapy against breast cancer | [173] |
Extracellular vesicles from mesenchymal stem cells | TNF-related apoptosis-inducing ligand (TRAIL) | Lung, breast, kidney cancer, pleural mesothelioma and neuroblastoma | [158] |
Exosomes from chronic myelogenous leukemia cells | TNF-related apoptosis-inducing ligand (TRAIL) | Enhance apoptosis in lymphoma | [159] |
Exosomes from HEK 293T | VSVG | Glioblastoma and liver cancer cells | [162] |
Exosomes from lymphoblast | Nef-E7 fusion protein | T lymphocytes immune response | [161] |
Exosomes from two mouse cell lines | Human MUC1 tumor antigen | Generate immune response against tumor | [157] |
Microvesicles from different cancer cell lines | DiD, carboxyfluorescein, paclitaxel, tirapazamine encapsulated in fusogenic liposomes | The same cancer cell lines used to produce microvesicles | [180] |
EVs Type | Nanotechnological Modification | Application | Reference |
---|---|---|---|
Exosomes from HEK 293T | Functionalization: CD9-HuR Load: miR-155 or CRISPR/Cas9 | Targeting and therapy of liver cancer | [186] |
Exosomes from HEK 293T | Functionalization: Lamp2b, fused to a fragment of IL-3 Load: Imatinib or BCR-ABL siRNA | Inhibition of chronic myeloid leukemia growth | [84] |
Exosomes from HEK 293T | Functionalization: GE 11 peptide Load: let-7a miRNA | Targeting and therapy of EGFR-expressing cancer tissues | [154] |
Exosomes from HEK 293T cells | Functionalization: BAP-TM receptor and biotin ligase BirA Load: viral capside | Gene therapy against glioma | [185] |
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Share and Cite
Susa, F.; Limongi, T.; Dumontel, B.; Vighetto, V.; Cauda, V. Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine. Cancers 2019, 11, 1979. https://doi.org/10.3390/cancers11121979
Susa F, Limongi T, Dumontel B, Vighetto V, Cauda V. Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine. Cancers. 2019; 11(12):1979. https://doi.org/10.3390/cancers11121979
Chicago/Turabian StyleSusa, Francesca, Tania Limongi, Bianca Dumontel, Veronica Vighetto, and Valentina Cauda. 2019. "Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine" Cancers 11, no. 12: 1979. https://doi.org/10.3390/cancers11121979