Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research
Abstract
:1. Introduction
1.1. Classification and Characteristics
1.2. Biological Function
1.3. Applications in Therapy
1.4. Applications in Diagnosis
2. Nanoparticle-Loaded Exosomes in Oncology
2.1. Superparamagnetic Iron Oxide and Ultrasmall Superparamagnetic Iron Oxide Nanoparticles
2.2. Quantum Dots
2.3. Gold Nanoparticles
2.4. Polymeric Nanoparticles
3. Transition Metal-Labeled Exosomes
4. Other Systems as Potential Cancer Diagnostic Tools
4.1. Bioluminiscent Agent-Loaded Evs
4.2. Nanocluster-Loaded Exosomes
4.3. Metabolic Labeled Exosomes
5. Exosomes Beyond Oncology
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Ref. | Labeling Strategy | Parent Cells | Exosome Isolation Method | Labeling Compound | Therapeutic Compound | Loading/Labeling Procedure | Surface Engineering | Detection Technique | Tests |
---|---|---|---|---|---|---|---|---|---|
[78] | Nanoparticle-loaded exosomes | Raw264.7 mouse macrophages | Sequential centrifugation | SPION | Curcumin | Exogenous (electroporation) | NRP-1 binding peptide by click chemistry | MRI | In vitro: U251 cells In vivo: BALB/c nude mice transplanted with U251 cells |
[79] | SKBR3 breast cancer cells | Exosome isolation kit | Gold-carbon QD | Exogenous (incubation exploiting targeted loading through anti-HER2 antibodies) | Fluorescence imaging | In vitro: HeLa cells | |||
[80] | MCF-7 breast cancer cells | Exosome isolation kit | Vanadium carbide QD | Exogenous (electroporation) | RGD peptide introduced by incubating exosomes with DSPE-PEG-RGD | Photoacoustic imaging | In vitro: MCF-7, A549, NHDF cells In vivo: tumor-bearing BALB/c nude mice | ||
[81] | Urine of gastric cancer patients | Sequential centrifugation | Chlorine-6 labeled gold NP | Exogenous (electroporation) | Fluorescence imaging | In vitro: MGC-803, Raw264.7 cells In vivo: MGC-803 tumor-bearing BALB/c-nude mice | |||
[82,83] | Murine adipose stem cells | Exosome isolation kit | USPION | Endogenous (cell incubation) | MRI | In vitro: exosomes immobilized in an agarose matrix In vivo: C57BL/6 mice | |||
[84] | Mesenchymal stem cells | Sequential centrifugation | Gold NP | Exogenous (incubation) | CT | In vivo: C57bl/6 mice | |||
[85] | Transition metal-labeled exosomes | Human umbilical cord mesenchymal stem cells | Sequential centrifugation | 68Gd (complexed by DOTA) | Exogenous (lipid insertion technique with Gd-DOTA-DSPE) | MRI | In vitro: K7M2 mouse and 14B human osteosarcoma cells In vivo: immunodeficient NU/NU nude mice implanted with K7M2 cells | ||
[86] | Human umbilical cord blood mononuclear cells | Sequential centrifugation | 64Cu (complexed by DOTA) | Exogenous (reaction between the maleimide group of DOTA and thiol groups on exosome surface) | PET/MRI | In vitro: HUVEC In vivo: C57BL/6J mice | |||
[87] | 4T1 breast cancer cells | Sequential centrifugation | 64Cu (complexed by NOTA) | Exogenous (reaction of NOTA with exosome surface proteins) | PEG decoration using PEG5k/NHS | PET | In vivo: 4T1 tumor-bearing BALB/c mice | ||
[88] | Mouse macrophage HEK293T cells | Sequential centrifugation | 99mTc | Exogenous (incubation with fac-[99mTc(CO)3(H2O)3]+) | DARPin G3 functionalization by transfection of the parent cells | Radioactive signal by gamma-counter | In vitro: SKOV-3, MCF-7, U87-MG, HT-29, A549 cells In vivo: BALB/c mice, SKOV-3 xenografted C57 nude mice | ||
[89] | Human embryonic kidney HEK293 cells | Sequential centrifugation | 111In | Exogenous (incubation with 111In -oxine) | CSPGAKVRC peptide, functionalized by transfection of the parent cells | CT/SPECT | In vitro: Raw264.7 cells In vivo: 4T1 tumor-bearing Balb/c mice | ||
[90] | Bioluminescently labeled exosomes | Human embryonic kidney 293T cells | Sequential centrifugation | Gaussia princeps luciferase (Gluc) | Endogenous (transfection of the parent cells with a gene encoding for Gluc bound to a membrane protein) | IVIS imaging | In vivo: immunodeficient athymic nude mice | ||
[91] | Human embryonic kidney 293T cells | Sequential centrifugation | GFP, tandem dimer Tomato | Endogenous (transfection of the parent cells with a gene encoding for palmGFP/palmtdTomato) | Multiphoton intravital microscopy | In vitro: 293T cells In vivo: C57BL6 (B6) mice implanted with mouse thymoma EL-4 cells | |||
[92] | Nanocluster loaded exosomes | HepG2 human hepatocellular carcinoma | Sequential centrifugation | Ag-nanoclusters and Fe3O4 NP | Endogenous (parent cells cultured in the presence of AgNO3 and FeCl2 forming the nanoclusters) | Flurescence bioimaging, CT, MRI | In vitro: HepG2, U87 cells | ||
[93] | Metabolic labeled exosomes | MDA-MB-231 breast cancer cells | Ultracentrifugation and size exclusion chromatography | Deuterium | Endogenous (parent cells cultured in presence of D2O/d-Gluc/d-Chol) | Raman spectroscopic imaging | In vitro: MDA-MB-231, MCF10A cells |
Ref. | Cell Line | Labeling Compound | Therapeutic Compound | Vesicle Preparation Method | Loading/Labeling Procedure | Detection Technique | Tests |
---|---|---|---|---|---|---|---|
[94] | Bel-7402 human hepatoma cancer cells | NP-encapsulated doxorubicin | NP-encapsulated doxorubicin | Coating of the NP with cell membranes through extrusion | Incubation | Fluorescence imaging | In vitro: Bel-7402, MCF-7, L-O2 cells |
[95] | J774A.1 mouse macrophages | Gd-conjugated liposomes | Sonication and extrusion of the exosome/liposome mixture | Obtained during vesicle preparation procedure | MRI | In vitro: K7M2, NIH/3T3 cells In vivo: osteosarcoma—bearing NU/NU immunodeficient mice | |
[96] | Raw264.7 mouse macrophages, HB1.F3 human neural stem cells | 99mTc-HMPAO | Sequential extrusion of parent cells and density gradient centrifugation | Incubation | SPECT/CT | In vivo: BALB/c mice |
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Ailuno, G.; Baldassari, S.; Lai, F.; Florio, T.; Caviglioli, G. Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research. Cells 2020, 9, 2569. https://doi.org/10.3390/cells9122569
Ailuno G, Baldassari S, Lai F, Florio T, Caviglioli G. Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research. Cells. 2020; 9(12):2569. https://doi.org/10.3390/cells9122569
Chicago/Turabian StyleAiluno, Giorgia, Sara Baldassari, Francesco Lai, Tullio Florio, and Gabriele Caviglioli. 2020. "Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research" Cells 9, no. 12: 2569. https://doi.org/10.3390/cells9122569