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
- Colombo, M.; Raposo, G.; Thery, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014, 30, 255–289. [Google Scholar] [CrossRef] [PubMed]
- Cocucci, E.; Racchetti, G.; Meldolesi, J. Shedding microvesicles: Artefacts no more. Trends Cell Biol. 2009, 19, 43–51. [Google Scholar] [CrossRef] [PubMed]
- Hristov, M.; Erl, W.; Linder, S.; Weber, P.C. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood 2004, 104, 2761–2766. [Google Scholar] [CrossRef] [PubMed]
- Raposo, G.; Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013, 200, 373–383. [Google Scholar] [CrossRef] [Green Version]
- Vlassov, A.V.; Magdaleno, S.; Setterquist, R.; Conrad, R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim. Biophys. Acta Gen. Subj. 2012, 1820, 940–948. [Google Scholar] [CrossRef]
- Denzer, K.; Kleijmeer, M.J.; Heijnen, H.F.G.; Stoorvogel, W.; Geuze, H.J. Exosome: From internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 2000, 113, 3365–3374. [Google Scholar]
- Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation—Association of plasma-membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987, 262, 9412–9420. [Google Scholar]
- Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Leijendekker, R.; Harding, C.V.; Melief, C.J.M.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996, 183, 1161–1172. [Google Scholar] [CrossRef]
- Thery, C.; Regnault, A.; Garin, J.; Wolfers, J.; Zitvogel, L.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Molecular characterization of dendritic cell-derived exosomes: Selective accumulation of the heat shock protein hsc73. J. Cell Biol. 1999, 147, 599–610. [Google Scholar] [CrossRef] [Green Version]
- Simpson, R.J.; Jensen, S.S.; Lim, J.W.E. Proteomic profiling of exosomes: Current perspectives. Proteomics 2008, 8, 4083–4099. [Google Scholar] [CrossRef]
- Hugel, B.; Carmen, M.; Martinez, M.C.; Kunzelmann, C.; Freyssinet, J.M. Membrane microparticles: Two sides of the coin. Physiology 2005, 20, 22–27. [Google Scholar] [CrossRef] [PubMed]
- Thery, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579. [Google Scholar] [CrossRef] [PubMed]
- Pontecorvi, G.; Bellenghi, M.; Puglisi, R.; Care, A.; Mattia, G. Tumor-derived extracellular vesicles and microRNAs: Functional roles, diagnostic, prognostic and therapeutic options. Cytokine Growth Factor Rev. 2020, 51, 75–83. [Google Scholar] [CrossRef] [PubMed]
- Bang, C.; Thum, T. Exosomes: New players in cell-cell communication. Int. J. Biochem. Cell Biol. 2012, 44, 2060–2064. [Google Scholar] [CrossRef] [PubMed]
- Bobrie, A.; Colombo, M.; Raposo, G.; Thery, C. Exosome secretion: Molecular mechanisms and roles in immune responses. Traffic 2011, 12, 1659–1668. [Google Scholar] [CrossRef] [PubMed]
- Chaput, N.; Thery, C. Exosomes: Immune properties and potential clinical implementations. Semin. Immunopathol. 2011, 33, 419–440. [Google Scholar] [CrossRef] [PubMed]
- Meldolesi, J. Exosomes and ectosomes in intercellular communication. Curr. Biol. 2018, 28, R435–R444. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bebelman, M.P.; Bun, P.; Huveneers, S.; van Niel, G.; Pegtel, D.M.; Verweij, F.J. Real-time imaging of multivesicular body-plasma membrane fusion to quantify exosome release from single cells. Nat. Protoc. 2020, 15, 102–121. [Google Scholar] [CrossRef]
- Parolini, I.; Federici, C.; Raggi, C.; Lugini, L.; Palleschi, S.; De Milito, A.; Coscia, C.; Iessi, E.; Logozzi, M.; Molinari, A.; et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J. Biol. Chem. 2009, 284, 34211–34222. [Google Scholar] [CrossRef] [Green Version]
- Fleming, A.; Sampey, G.; Chung, M.C.; Bailey, C.; van Hoek, M.L.; Kashanchi, F.; Hakami, R.M. The carrying pigeons of the cell: Exosomes and their role in infectious diseases caused by human pathogens. Pathog. Dis. 2014, 71, 107–118. [Google Scholar] [CrossRef] [Green Version]
- Kimura, K.; Hohjoh, H.; Fukuoka, M.; Sato, W.; Oki, S.; Tomi, C.; Yamaguchi, H.; Kondo, T.; Takahashi, R.; Yamamura, T. Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis. Nat. Commun. 2018, 9. [Google Scholar] [CrossRef]
- Gon, Y.; Shimizu, T.; Mizumura, K.; Maruoka, S.; Hikichi, M. Molecular techniques for respiratory diseases: MicroRNA and extracellular vesicles. Respirology 2020, 25, 149–160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sasaki, R.; Kanda, T.; Yokosuka, O.; Kato, N.; Matsuoka, S.; Moriyama, M. Exosomes and hepatocellular carcinoma: From bench to bedside. Int. J. Mol. Sci. 2019, 20, 1406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abak, A.; Abhari, A.; Rahimzadeh, S. Exosomes in cancer: Small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics. PEERJ 2018, 6, e4763. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 2008, 10, 619–624. [Google Scholar] [CrossRef]
- Ristorcelli, E.; Beraud, E.; Verrando, P.; Villard, C.; Lafitte, D.; Sbarra, V.; Lombardo, D.; Verine, A. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J. 2008, 22, 3358–3369. [Google Scholar] [CrossRef]
- Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes. Nat. Med. 1998, 4, 594–600. [Google Scholar] [CrossRef]
- Umezu, T.; Ohyashiki, K.; Kuroda, M.; Ohyashiki, J.H. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene 2013, 32, 2747–2755. [Google Scholar] [CrossRef] [Green Version]
- Gajos-Michniewicz, A.; Duechler, M.; Czyz, M. MiRNA in melanoma-derived exosomes. Cancer Lett. 2014, 347, 29–37. [Google Scholar] [CrossRef]
- Gerloff, D.; Lutzkendorf, J.; Moritz, R.K.C.; Wersig, T.; Mader, K.; Muller, L.P.; Sunderkotter, C. Melanoma-derived exosomal miR-125b-5p educates tumor associated macrophages (TAMs) by targeting lysosomal acid lipase A (LIPA). Cancers 2020, 12, 464. [Google Scholar] [CrossRef] [Green Version]
- Kurahashi, R.; Kadomatsu, T.; Baba, M.; Hara, C.; Itoh, H.; Miyata, K.; Endo, M.; Morinaga, J.; Terada, K.; Araki, K.; et al. MicroRNA-204-5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma. Cancer Sci. 2019, 110, 1897–1908. [Google Scholar] [CrossRef] [Green Version]
- Chalmin, F.; Ladoire, S.; Mignot, G.; Vincent, J.; Bruchard, M.; Remy-Martin, J.P.; Boireau, W.; Rouleau, A.; Simon, B.; Lanneau, D.; et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Investig. 2010, 120, 457–471. [Google Scholar] [CrossRef] [PubMed]
- Ratajczak, J.; Wysoczynski, M.; Hayek, F.; Janowska-Wieczorek, A.; Ratajczak, M.Z. Membrane-derived microvesicles: Important and underappreciated mediators of cell-to-cell communication. Leukemia 2006, 20, 1487–1495. [Google Scholar] [CrossRef]
- Jung, T.; Castellana, D.; Klingbeil, P.; Hernandez, I.C.; Vitacolonna, M.; Orlicky, D.J.; Roffler, S.; Brodt, P.; Zoller, M. CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 2009, 11, 1093–1150. [Google Scholar] [CrossRef] [Green Version]
- Lima, L.G.; Chammas, R.; Monteiro, R.Q.; Moreira, M.E.C.; Barcinski, M.A. Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett. 2009, 283, 168–175. [Google Scholar] [CrossRef] [PubMed]
- Hood, J.L.; Roman, S.S.; Wickline, S.A. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011, 71, 3792–3801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peinado, H.; Kovic, M.A.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; Garcia-Santos, G.; Ghajar, C.M.; et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET (vol 18, pg 883, 2012). Nat. Med. 2012, 18, 883–891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, J.; Afshari, A.; Sengupta, R.; Sebastiano, V.; Gupta, A.; Kim, Y.H.; Biol, R.P.C. Replication study: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Elife 2018, 7, e39944. [Google Scholar] [CrossRef] [PubMed]
- Ramteke, A.; Ting, H.; Agarwal, C.; Mateen, S.; Somasagara, R.; Hussain, A.; Graner, M.; Frederick, B.; Agarwal, R.; Deep, G. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol. Carcinog. 2015, 54, 554–565. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.H.; Luo, Y.M.; He, W.; Zhao, Y.; Kong, Y.; Liu, H.W.; Zhong, G.Z.; Li, Y.T.; Li, J.; Huang, J.; et al. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. J. Clin. Investig. 2020, 130, 404–421. [Google Scholar] [CrossRef]
- Zhou, W.Y.; Fong, M.Y.; Min, Y.F.; Somlo, G.; Liu, L.; Palomares, M.R.; Yu, Y.; Chow, A.; O’Connor, S.T.F.; Chin, A.R.; et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014, 25, 501–515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fong, M.Y.; Zhou, W.Y.; Liu, L.; Alontaga, A.Y.; Chandra, M.; Ashby, J.; Chow, A.; O’Connor, S.T.F.; Li, S.S.; Chin, A.R.; et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat. Cell Biol. 2015, 17, 183–194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Le, M.T.N.; Hamar, P.; Guo, C.Y.; Basar, E.; Perdigao-Henriques, R.; Balaj, L.; Lieberman, J. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J. Clin. Investig. 2014, 124, 5109–5128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, M.; Zhao, C.; Shi, H.; Zhang, B.; Zhang, L.; Zhang, X.; Wang, S.; Wu, X.; Yang, T.; Huang, F.; et al. Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: Novel biomarkers and a mechanism for gastric cancer. Br. J. Cancer 2014, 110, 1199–1210. [Google Scholar] [CrossRef]
- Lim, W.; Kim, H.S. Exosomes as Therapeutic Vehicles for Cancer. Tissue Eng. Regen. Med. 2019, 16, 213–223. [Google Scholar] [CrossRef]
- Antimisiaris, S.G.; Mourtas, S.; Marazioti, A. Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics 2018, 10, 218. [Google Scholar] [CrossRef] [Green Version]
- Qiao, L.; Hu, S.Q.; Huang, K.; Su, T.; Li, Z.H.; Vandergriff, A.; Cores, J.; Dinh, P.U.; Allen, T.; Shen, D.L.; et al. Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics 2020, 10, 3474–3487. [Google Scholar] [CrossRef]
- Lu, M.; Huang, Y.Y. Bioinspired exosome-like therapeutics and delivery nanoplatforms. Biomaterials 2020, 242, 119925. [Google Scholar] [CrossRef]
- Sato, Y.T.; Umezaki, K.; Sawada, S.; Mukai, S.; Sasaki, Y.; Harada, N.; Shiku, H.; Akiyoshi, K. Engineering hybrid exosomes by membrane fusion with liposomes. Sci. Rep. 2016, 6, 21933. [Google Scholar] [CrossRef] [Green Version]
- Jang, S.C.; Kim, O.Y.; Yoon, C.M.; Choi, D.S.; Roh, T.Y.; Park, J.; Nilsson, J.; Lotvall, J.; Kim, Y.K.; Gho, Y.S. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 2013, 7, 7698–7710. [Google Scholar] [CrossRef]
- Johnsen, K.B.; Gudbergsson, J.M.; Skov, M.N.; Pilgaard, L.; Moos, T.; Duroux, M. A comprehensive overview of exosomes as drug delivery vehicles—Endogenous nanocarriers for targeted cancer therapy. Biochim. Biophys. Acta Rev. Cancer 2014, 1846, 75–87. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.F.; Shi, J.B.; Li, C. Small extracellular vesicle loading systems in cancer therapy: Current status and the way forward. Cytotherapy 2019, 21, 1122–1136. [Google Scholar] [CrossRef] [PubMed]
- Srivastava, A.; Amreddy, N.; Babu, A.; Panneerselvam, J.; Mehta, M.; Muralidharan, R.; Chen, A.; Zhao, Y.D.; Razaq, M.; Riedinger, N.; et al. Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells. Sci. Rep. 2016, 6, 38541. [Google Scholar] [CrossRef] [PubMed]
- Ye, H.; Wang, K.Y.; Lu, Q.; Zhao, J.; Wang, M.L.; Kan, Q.M.; Zhang, H.T.; Wang, Y.J.; He, Z.G.; Sun, J. Nanosponges of circulating tumor-derived exosomes for breast cancer metastasis inhibition. Biomaterials 2020, 242, 119932. [Google Scholar] [CrossRef]
- Li, Y.J.; Wu, J.Y.; Wang, J.M.; Hu, X.B.; Cai, J.X.; Xiang, D.X. Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. Acta Biomater. 2020, 101, 519–530. [Google Scholar] [CrossRef]
- Haney, M.J.; Zhao, Y.L.; Jin, Y.S.; Li, S.M.; Bago, J.R.; Klyachko, N.L.; Kabanov, A.V.; Batrakova, E.V. Macrophage-derived extracellular vesicles as drug delivery systems for triple negative breast cancer (TNBC) therapy. J. Neuroimmune Pharmacol. 2020, 15, 487–500. [Google Scholar] [CrossRef]
- Tran, P.H.L.; Wang, T.; Yin, W.; Tran, T.T.D.; Nguyen, T.N.G.; Lee, B.J.; Duan, W. Aspirin-loaded nanoexosomes as cancer therapeutics. Int. J. Pharm. 2019, 572, 118786. [Google Scholar] [CrossRef]
- Lin, Q.; Qu, M.K.; Zhou, B.J.; Patra, H.K.; Sun, Z.H.; Luo, Q.; Yang, W.Y.; Wu, Y.C.; Zhang, Y.; Li, L.; et al. Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine. J. Control Release 2019, 311, 104–116. [Google Scholar] [CrossRef]
- Baldari, S.; Di Rocco, G.; Magenta, A.; Picozza, M.; Toietta, G. Extracellular vesicles-encapsulated MicroRNA-125b produced in genetically modified mesenchymal stromal cells inhibits hepatocellular carcinoma cell proliferation. Cells 2019, 8, 1560. [Google Scholar] [CrossRef] [Green Version]
- Nie, H.F.; Xie, X.D.; Zhang, D.D.; Zhou, Y.; Li, B.F.; Li, F.Q.; Li, F.Y.; Cheng, Y.L.; Mei, H.; Meng, H.; et al. Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer. Nanoscale 2020, 12, 877–887. [Google Scholar] [CrossRef]
- Wang, H.B.; Wei, H.; Wang, J.S.; Li, L.; Chen, A.Y.; Li, Z.G. MicroRNA-181d-5p-containing exosomes derived from CAFs promote EMT by regulating CDX2/HOXA5 in breast cancer. Mol. Ther. Nucleic Acids 2020, 19, 654–667. [Google Scholar] [CrossRef] [PubMed]
- Liang, G.F.; Zhu, Y.L.; Ali, D.J.; Tian, T.; Xu, H.T.; Si, K.; Sun, B.; Chen, B.A.; Xiao, Z.D. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J. Nanobiotechnol. 2020, 18, 10. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.J.; Liu, J.Q.; Zhang, Q.L.; Liu, B.X.; Cheng, Y.; Zhang, Y.L.; Sun, Y.N.; Ge, H.; Liu, Y.Q. Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3. J. Exp. Clin. Cancer Res. 2020, 39, 65. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, M.; Sawada, K.; Miyamoto, M.; Shimizu, A.; Yamamoto, M.; Kinose, Y.; Nakamura, K.; Kawano, M.; Kodama, M.; Hashimoto, K.; et al. Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer. Biochem. Biophys. Res. Commun. 2020, 527, 153–161. [Google Scholar] [CrossRef] [PubMed]
- Forterre, A.V.; Wang, J.H.; Delcayre, A.; Kim, K.; Green, C.; Pegram, M.D.; Jeffrey, S.S.; Matin, A.C. Extracellular vesicle-mediated in vitro transcribed mRNA delivery for treatment of HER2(+) breast cancer xenografts in mice by prodrug CB1954 without general toxicity. Mol. Cancer Ther. 2020, 19, 858–867. [Google Scholar] [CrossRef] [Green Version]
- Zhuang, M.J.; Chen, X.L.; Du, D.; Shi, J.M.; Deng, M.; Long, Q.; Yin, X.F.; Wang, Y.Y.; Rao, L. SPION decorated exosome delivery of TNF-alpha to cancer cell membranes through magnetism. Nanoscale 2020, 12, 173–188. [Google Scholar] [CrossRef]
- Xin, L.; Yuan, Y.W.; Liu, C.; Zhou, L.Q.; Liu, L.; Zhou, Q.; Li, S.H. Preparation of internalizing RGD-modified recombinant methioninase exosome active targeting vector and antitumor effect evaluation. Dig. Dis. Sci. 2020. [Google Scholar] [CrossRef]
- Huang, T.; Deng, C.X. Current progresses of exosomes as cancer diagnostic and prognostic biomarkers. Int. J. Biol. Sci. 2019, 15, 1–11. [Google Scholar] [CrossRef]
- van der Meel, R.; Krawczyk-Durka, M.; van Solinge, W.W.; Schiffelers, R.M. Toward routine detection of extracellular vesicles in clinical samples. Int. J. Lab. Hematol. 2014, 36, 244–253. [Google Scholar] [CrossRef]
- Shao, H.L.; Chung, J.; Lee, K.; Balaj, L.; Min, C.; Carter, B.S.; Hochberg, F.H.; Breakefield, X.O.; Lee, H.; Weissleder, R. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat. Commun. 2015, 6, 6999. [Google Scholar] [CrossRef] [Green Version]
- Kosaka, N.; Iguchi, H.; Ochiya, T. Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010, 101, 2087–2092. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Zheng, Q.P.; Bao, C.Y.; Li, S.Y.; Guo, W.J.; Zhao, J.; Chen, D.; Gu, J.R.; He, X.H.; Huang, S.L. Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis. Cell Res. 2015, 25, 981–984. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, D.S.; Kim, D.K.; Kim, Y.K.; Gho, Y.S. Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom. Rev. 2015, 34, 474–490. [Google Scholar] [CrossRef] [PubMed]
- Verma, M.; Lam, T.K.; Hebert, E.; Divi, R.L. Extracellular vesicles: Potential applications in cancer diagnosis, prognosis, and epidemiology. BMC Clin. Pathol. 2015, 15, 6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zong, S.F.; Zong, J.Z.; Chen, C.; Jiang, X.Y.; Zhang, Y.Z.; Wang, Z.Y.; Cui, Y.P. Single molecule localization imaging of exosomes using blinking silicon quantum dots. Nanotechnology 2018, 29, 065705. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.; Zong, S.F.; Wang, Z.Y.; Lu, J.; Zhu, D.; Zhang, Y.Z.; Cui, Y.P. Imaging and intracellular tracking of cancer-derived exosomes using single-molecule localization-based super-resolution microscope. ACS Appl. Mater. Interfaces 2016, 8, 25825–25833. [Google Scholar] [CrossRef]
- Shang, M.Y.; Ji, J.S.; Song, C.; Gao, B.J.; Jin, J.G.; Kuo, W.P.; Kang, H.J. Extracellular vesicles: A brief overview and its role in precision medicine. In Extracellular Vesicles: Methods and Protocols; Kuo, W.P., Jia, S., Eds.; Humana Press: New York, NY, USA, 2017; Volume 1660, pp. 1–14. [Google Scholar]
- Jia, G.; Han, Y.; An, Y.L.; Ding, Y.A.; He, C.; Wang, X.H.; Tang, Q.S. NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials 2018, 178, 302–316. [Google Scholar] [CrossRef]
- Jiang, X.Y.; Zong, S.F.; Chen, C.; Zhang, Y.Z.; Wang, Z.Y.; Cui, Y.P. Gold-carbon dots for the intracellular imaging of cancer-derived exosomes. Nanotechnology 2018, 29, 175701. [Google Scholar] [CrossRef]
- Cao, Y.; Wu, T.T.; Zhang, K.; Meng, X.D.; Dai, W.H.; Wang, D.D.; Dong, H.F.; Zhang, X.J. Engineered exosome-mediated near-infrared-II region V2C quantum dot delivery for nucleus-target low-temperature photothermal therapy. ACS Nano 2019, 13, 1499–1510. [Google Scholar] [CrossRef]
- Pan, S.J.; Pei, L.J.; Zhang, A.M.; Zhang, Y.H.; Zhang, C.L.; Huang, M.; Huang, Z.C.; Liu, B.; Wang, L.R.; Ma, L.J.; et al. Passion fruit-like exosome-PMA/Au-BSA@Ce6 nanovehicles for real-time fluorescence imaging and enhanced targeted photodynamic therapy with deep penetration and superior retention behavior in tumor. Biomaterials 2020, 230, 119606. [Google Scholar] [CrossRef]
- Busato, A.; Bonafede, R.; Bontempi, P.; Scambi, I.; Schiaffino, L.; Benati, D.; Malatesta, M.; Sbarbati, A.; Marzola, P.; Mariotti, R. Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: A new method to obtain labeled exosomes. Int. J. Nanomed. 2016, 11, 2481–2490. [Google Scholar]
- Busato, A.; Bonafede, R.; Bontempi, P.; Scambi, I.; Schiaffino, L.; Benati, D.; Malatesta, M.; Sbarbati, A.; Marzola, P.; Mariotti, R. Labeling and magnetic resonance imaging of exosomes isolated from adipose stem cells. Curr. Protoc. Cell Biol. 2017, 75. [Google Scholar] [CrossRef] [PubMed]
- Betzer, O.; Perets, N.; Ange, A.; Motiei, M.; Sadan, T.; Yadid, G.; Offen, D.; Popovtzer, R. In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles. ACS Nano 2017, 11, 10883–10893. [Google Scholar] [CrossRef] [PubMed]
- Abello, J.; Nguyen, T.D.T.; Marasini, R.; Aryal, S.; Weiss, M.L. Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice. Theranostics 2019, 9, 2325–2345. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, A.; Alves, V.; Rondao, T.; Sereno, J.; Neves, A.; Lino, M.; Ribeiro, A.; Abrunhosa, A.J.; Ferreira, L.S. A positron-emission tomography (PET)/magnetic resonance imaging (MRI) platform to track in vivo small extracellular vesicles. Nanoscale 2019, 11, 13243–13248. [Google Scholar] [CrossRef] [Green Version]
- Shi, S.X.; Li, T.T.; Wen, X.F.; Wu, S.Y.; Xiong, C.Y.; Zhao, J.; Lincha, V.R.; Chow, D.S.; Liu, Y.Y.; Sood, A.K.; et al. Copper-64 labeled PEGylated exosomes for in vivo positron emission tomography and enhanced tumor retention. Bioconjugate Chem. 2019, 30, 2675–2683. [Google Scholar] [CrossRef] [PubMed]
- Molavipordanjani, S.; Khodashenas, S.; Abedi, S.M.; Moghadam, M.F.; Mardanshahi, A.; Hosseinimehr, S.J. Tc-99m-radiolabeled HER2 targeted exosome for tumor imaging. Eur. J. Pharm. Sci. 2020, 148, 105312. [Google Scholar] [CrossRef]
- Rashid, M.H.; Borin, T.F.; Ara, R.; Alptekin, A.; Liu, Y.T.; Arbab, A.S. Generation of novel diagnostic and therapeutic exosomes to detect and deplete protumorigenic M2 macrophages. Adv. Ther. 2020, 3, 1900209. [Google Scholar] [CrossRef]
- Lai, C.P.; Tannous, B.A.; Breakefield, X.O. Noninvasive in vivo monitoring of extracellular vesicles. Biolumin. Imaging Methods Protoc. 2014, 1098, 249–258. [Google Scholar]
- Lai, C.P.; Kim, E.Y.; Badr, C.E.; Weissleder, R.; Mempel, T.R.; Tannous, B.A.; Breakefield, X.O. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat. Commun. 2015, 6, 7029. [Google Scholar] [CrossRef]
- Tayyaba; Rehman, F.U.; Shaikh, S.; Semcheddine, F.; Du, T.Y.; Jiang, H.; Wang, X.M. In situ self-assembled Ag-Fe3O4 nanoclusters in exosomes for cancer diagnosis. J. Mater. Chem. B 2020, 8, 2845–2855. [Google Scholar]
- Horgan, C.C.; Nagelkerke, A.; Whittaker, T.E.; Nele, V.; Massi, L.; Kauscher, U.; Penders, J.; Bergholt, M.S.; Hood, S.R.; Stevens, M.M. Molecular imaging of extracellular vesicles in vitro via Raman metabolic labelling. J. Mater. Chem. B 2020, 8, 4447–4459. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.F.; Zhang, F.; Wang, K.; Luo, P.C.; Wei, Y.Q.; Liu, S.Q. Activatable fluorescence imaging and targeted drug delivery via extracellular vesicle-like porous coordination polymer nanoparticles. Anal. Chem. 2019, 91, 14036–14042. [Google Scholar] [CrossRef] [PubMed]
- Rayamajhi, S.; Marasini, R.; Nguyen, T.D.T.; Plattner, B.L.; Biller, D.; Aryal, S. Strategic reconstruction of macrophage-derived extracellular vesicles as a magnetic resonance imaging contrast agent. Biomater. Sci. 2020, 8, 2887–2904. [Google Scholar] [CrossRef] [PubMed]
- Hwang, D.W.; Choi, H.; Jang, S.C.; Yoo, M.Y.; Park, J.Y.; Choi, N.E.; Oh, H.J.; Ha, S.; Lee, Y.S.; Jeong, J.M.; et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using Tc-99m-HMPAO. Sci. Rep. 2015, 5, 15636. [Google Scholar] [CrossRef]
- Gupta, A.K.; Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005, 26, 3995–4021. [Google Scholar] [CrossRef]
- Aggarwal, B.B.; Kumar, A.; Bharti, A.C. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003, 23, 363–398. [Google Scholar]
- Luthra, P.M.; Lal, N. Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma. Eur. J. Med. Chem. 2016, 109, 23–35. [Google Scholar] [CrossRef]
- Hamerlik, P.; Lathia, J.D.; Rasmussen, R.; Wu, Q.L.; Bartkova, J.; Lee, M.; Moudry, P.; Bartek, J.; Fischer, W.; Lukas, J.; et al. Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J. Exp. Med. 2012, 209, 507–520. [Google Scholar] [CrossRef] [Green Version]
- Laurent, S.; Dutz, S.; Hafeli, U.O.; Mahmoudi, M. Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Adv. Colloid Interface Sci. 2011, 166, 8–23. [Google Scholar] [CrossRef]
- Ciravolo, V.; Huber, V.; Ghedini, G.C.; Venturelli, E.; Bianchi, F.; Campiglio, M.; Morelli, D.; Villa, A.; Della Mina, P.; Menard, S.; et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J. Cell. Physiol. 2012, 227, 658–667. [Google Scholar] [CrossRef] [PubMed]
- Huhn, J.; Carrillo-Carrion, C.; Soliman, M.G.; Pfeiffer, C.; Valdeperez, D.; Masood, A.; Chakraborty, I.; Zhu, L.; Gallego, M.; Yue, Z.; et al. Selected standard protocols for the synthesis, phase transfer, and characterization of inorganic colloidal nanoparticles. Chem. Mater. 2017, 29, 399–461. [Google Scholar] [CrossRef]
- Rogosnitzky, M.; Branch, S. Gadolinium-based contrast agent toxicity: A review of known and proposed mechanisms. Biometals 2016, 29, 365–376. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gray, W.D.; French, K.M.; Ghosh-Choudhary, S.; Maxwell, J.T.; Brown, M.E.; Platt, M.O.; Searles, C.D.; Davis, M.E. Identification of therapeutic covariant MicroRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ. Res. 2015, 116, 255–263. [Google Scholar] [CrossRef] [Green Version]
- Limoni, S.K.; Moghadam, M.F.; Moazzeni, S.M.; Gomari, H.; Salimi, F. Engineered exosomes for targeted transfer of siRNA to HER2 positive breast cancer cells. Appl. Biochem. Biotechnol. 2019, 187, 352–364. [Google Scholar] [CrossRef]
- Arbab, A.S.; Thiffault, C.; Navia, B.; Victor, S.J.; Hong, K.; Zhang, L.; Jiang, Q.; Varma, N.R.S.; Iskander, A.S.M.; Chopp, M. Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging. BMC Med. Imaging 2012, 12, 33. [Google Scholar] [CrossRef] [Green Version]
- Tannous, B.A.; Kim, D.E.; Fernandez, J.L.; Weissleder, R.; Breakefield, X.O. Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol. Ther. 2005, 11, 435–443. [Google Scholar] [CrossRef]
- Morris, L.M.; Klanke, C.A.; Lang, S.A.; Lim, F.Y.; Crombleholme, T.M. TdTomato and EGFP identification in histological sections: Insight and alternatives. Biotech. Histochem. 2010, 85, 379–387. [Google Scholar] [CrossRef]
- Shaikh, S.; Rehman, F.U.; Du, T.Y.; Jiang, H.; Yin, L.H.; Wang, X.M.; Chai, R.J. Real-time multimodal bioimaging of cancer cells and exosomes through biosynthesized iridium and iron nanoclusters. ACS Appl. Mater. Interfaces 2018, 10, 26056–26063. [Google Scholar] [CrossRef]
- Kallepitis, C.; Bergholt, M.S.; Mazo, M.M.; Leonardo, V.; Skaalure, S.C.; Maynard, S.A.; Stevens, M.M. Quantitative volumetric Raman imaging of three dimensional cell cultures. Nat. Commun. 2017, 8, 14843. [Google Scholar] [CrossRef] [Green Version]
- Rad, A.M.; Arbab, A.S.; Iskander, A.S.M.; Jiang, Q.; Soltanian-Zadeh, H. Quantification of superparamagenetic iron oxide (SPIO)-labeled cells using MRI. J. Magn. Reson. Imaging 2007, 26, 366–374. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thery, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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
APA StyleAiluno, G., Baldassari, S., Lai, F., Florio, T., & Caviglioli, G. (2020). Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research. Cells, 9(12), 2569. https://doi.org/10.3390/cells9122569