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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

The Promising Role of Natural Exosomal Nanoparticles in Cancer Chemoimmunotherapy

Author(s): Archana Premnath, Sonu Benny, Aneesh Thankappan Presanna* and Sabitha Mangalathillam*

Volume 23, Issue 9, 2022

Published on: 10 August, 2022

Page: [723 - 734] Pages: 12

DOI: 10.2174/1389200223666220627103213

Price: $65

Abstract

Exosomal nanoparticles are cell-derived nano-sized vesicles in the size range of 30-150nm formed by the inward infolding of the cell membrane. They are encased in a lipid bilayer membrane and contain various proteins and nucleic acids according to the characteristics of their parent cell. They are involved in intercellular communication. Their specific structural and inherent properties are helpful in therapeutics and as biomarkers in diagnostics. Since they are biomimetic, these small-sized nanoparticles pose many advantages if used as a drug carrier vehicle. In cancer, the exosomal nanoparticles have both stimulatory and inhibitory activity towards immune responses; hence, they are used in immunotherapy. They can also carry chemotherapeutic agents to the target site minimizing their targetability concerns. Chemoimmunotherapy (CIT) is a synergistic approach in which chemotherapy and immunotherapy are utilized to benefit each other. Exosomal nanoparticles (NPs) are essential in delivering CIT agents into tumor tissues. Most advanced studies in CIT take place in the stimulator of interferon genes (STING) signaling pathway, where the STING activation supported by chemotherapy-induced an increase in immune surveillance through the help of exosomal NPs. Dendritic cell(DC) derived exosomes, as well as Mesenchymal stem cells (MSC), are abundantly used in immunotherapy, and hence their support can be used in chemoimmunotherapy (CIT) for multifaceted benefits.

Keywords: Exosome, nanoparticles, cancer, chemotherapy, immunotherapy, chemoimmunotherapy, dendritic cells, mesenchymal stem cell.

Graphical Abstract
[1]
Patra, J.K.; Das, G.; Fraceto, L.F.; Estefania, V.R.C.; Maria, D.P.R-T.; Acosta-Torres, L.S. Nano based drug delivery systems: Recent devel-opments and future prospects. J. Nanobiotechnology, 2018, 16, 1-33.
[2]
Yan, W.; Jiang, S. Immune cell-derived exosomes in the cancer-immunity cycle. Trends Cancer, 2020, 6(6), 506-517.
[http://dx.doi.org/10.1016/j.trecan.2020.02.013] [PMID: 32460004]
[3]
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(19), 9412-9420.
[http://dx.doi.org/10.1016/S0021-9258(18)48095-7] [PMID: 3597417]
[4]
Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9(6), 654-659.
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[5]
Kurian, T.K.; Banik, S.; Gopal, D.; Chakrabarti, S.; Mazumder, N. Elucidating methods for isolation and quantification of exosomes: A review. Mol. Biotechnol., 2021, 63(4), 249-266.
[http://dx.doi.org/10.1007/s12033-021-00300-3] [PMID: 33492613]
[6]
Patil, S.M.; Sawant, S.S.; Kunda, N.K. Exosomes as drug delivery systems: A brief overview and progress update. Eur. J. Pharm. Biopharm., 2020, 154, 259-269.
[http://dx.doi.org/10.1016/j.ejpb.2020.07.026] [PMID: 32717385]
[7]
Subra, C.; Grand, D.; Laulagnier, K.; Stella, A.; Lambeau, G.; Paillasse, M.; De Medina, P.; Monsarrat, B.; Perret, B.; Silvente-Poirot, S.; Poirot, M.; Record, M. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J. Lipid Res., 2010, 51(8), 2105-2120.
[http://dx.doi.org/10.1194/jlr.M003657] [PMID: 20424270]
[8]
Mathivanan, S.; Fahner, C.J.; Reid, G.E.; Simpson, R.J. ExoCarta 2012: Database of exosomal proteins, RNA and lipids. Nucleic Acids Res., 2012, 40, D1241-D1244.
[http://dx.doi.org/10.1093/nar/gkr828] [PMID: 21989406]
[9]
Simpson, R.J.; Kalra, H.; Mathivanan, S. ExoCarta as a resource for exosomal research. J. Extracell. Vesicles, 2012, 1(1), 1-6.
[http://dx.doi.org/10.3402/jev.v1i0.18374] [PMID: 24009883]
[10]
Cubaddaa, F.; Brian, P.; Cottinghamc, K.L. HHS Public Access. Physiol. Behav., 2017, 176, 139-148.
[11]
Fontana, S.; Saieva, L.; Taverna, S.; Alessandro, R. Contribution of proteomics to understanding the role of tumor-derived exosomes in can-cer progression: State of the art and new perspectives. Proteomics, 2013, 13(10-11), 1581-1594.
[http://dx.doi.org/10.1002/pmic.201200398] [PMID: 23401131]
[12]
Ciardiello, C.; Cavallini, L.; Spinelli, C.; Yang, J.; Reis-Sobreiro, M.; de Candia, P.; Minciacchi, V.R.; Di Vizio, D. Focus on extracellular vesi-cles: New frontiers of cell-to-cell communication in cancer. Int. J. Mol. Sci., 2016, 17(2), 175.
[http://dx.doi.org/10.3390/ijms17020175] [PMID: 26861306]
[13]
Zhang, Y.; Bi, J.; Huang, J.; Tang, Y.; Du, S.; Li, P. Exosome: A review of its classification, isolation techniques, storage, diagnostic and tar-geted therapy applications. Int. J. Nanomedicine, 2020, 15, 6917-6934.
[http://dx.doi.org/10.2147/IJN.S264498] [PMID: 33061359]
[14]
Pascucci, L.; Coccè, V.; Bonomi, A.; Ami, D.; Ceccarelli, P.; Ciusani, E.; Viganò, L.; Locatelli, A.; Sisto, F.; Doglia, S.M.; Parati, E.; Bernardo, M.E.; Muraca, M.; Alessandri, G.; Bondiolotti, G.; Pessina, A. Paclitaxel is incorporated by mesenchymal stromal cells and released in exo-somes that inhibit in vitro tumor growth: A new approach for drug delivery. J. Control. Release, 2014, 192, 262-270.
[http://dx.doi.org/10.1016/j.jconrel.2014.07.042] [PMID: 25084218]
[15]
Gilligan, K.E.; Dwyer, R.M. Engineering exosomes for cancer therapy. Int. J. Mol. Sci., 2017, 18(6), 1122.
[http://dx.doi.org/10.3390/ijms18061122] [PMID: 28538671]
[16]
Morishita, M.; Takahashi, Y.; Nishikawa, M.; Takakura, Y. Pharmacokinetics of exosomes-an important factor for elucidating the biological roles of exosomes and for the development of exosome-based therapeutics. J. Pharm. Sci., 2017, 106(9), 2265-2269.
[http://dx.doi.org/10.1016/j.xphs.2017.02.030] [PMID: 28283433]
[17]
Kim, D.H.; Kothandan, V.K.; Kim, H.W.; Kim, K.S.; Kim, J.Y.; Cho, H.J.; Lee, Y.; Lee, D-E.; Hwang, S.R. Noninvasive assessment of exo-some pharmacokinetics in vivo: A review. Pharmaceutics, 2019, 11(12), 1-11.
[http://dx.doi.org/10.3390/pharmaceutics11120649]
[18]
Gurunathan, S.; Kang, M.H.; Kim, J.H. A comprehensive review on factors influences biogenesis, functions, therapeutic and clinical implica-tions of exosomes. Int. J. Nanomedicine, 2021, 16, 1281-1312.
[http://dx.doi.org/10.2147/IJN.S291956] [PMID: 33628021]
[19]
Peng, H.; Ji, W.; Zhao, R.; Yang, J.; Lu, Z.; Li, Y.; Zhang, X. Exosome: A significant nano-scale drug delivery carrier. J. Mater. Chem. B Mater. Biol. Med., 2020, 8(34), 7591-7608.
[http://dx.doi.org/10.1039/D0TB01499K] [PMID: 32697267]
[20]
Xu, M.; Yang, Q.; Sun, X.; Wang, Y. Recent advancements in the loading and modification of therapeutic exosomes. Front. Bioeng. Biotechnol., 2020, 8, 586130.
[21]
Edwin, J.; Wang, W.; Yin, T.Y. Recent advancements in the use of exosomes as drug delivery systems 06 Biological Sciences 0601 Biochem-istry and Cell Biology. J. Nanobiotechnology, 2018, 16, 1-13.
[22]
Nazarenko, I.; Rupp, A.K.; Altevogt, P. Exosomes as a potential tool for a specific delivery of functional molecules. Methods Mol. Biol., 2013, 1049, 495-511.
[http://dx.doi.org/10.1007/978-1-62703-547-7_37] [PMID: 23913240]
[23]
Wang, X.; Zhang, H.; Yang, H.; Bai, M.; Ning, T.; Li, S.; Li, J.; Deng, T.; Ying, G.; Ba, Y. Cell-derived exosomes as promising carriers for drug delivery and targeted therapy. Curr. Cancer Drug Targets, 2018, 18(4), 347-354.
[http://dx.doi.org/10.2174/1568009617666170710120311] [PMID: 28699500]
[24]
Kim, Y.K.; Choi, Y.; Nam, G.H.; Kim, I.S. Functionalized exosome harboring bioactive molecules for cancer therapy. Cancer Lett., 2020, 489, 155-162.
[http://dx.doi.org/10.1016/j.canlet.2020.05.036] [PMID: 32623071]
[25]
Palacios-Ferrer, L.; Garcia-Ortega, M.B.; Gallardo-Gomez, M.; Garcia, M.A.; Diaz, C.; Boulaiz, H.; Valdivia, J.; Jurado, J.M.; Almazan-Fernandez, F.M.; Arias-Santiago, S.; Amezcua, V.; Peinado, H.; Vicente, F.; Del Palacio, J.P.; Marchal, J.A. Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol. Oncol., 2021, 15(2), 407-428.
[26]
Liu, J.; Ren, L.; Li, S.; Li, W.; Zheng, X.; Yang, Y.; Fu, W.; Yi, J.; Wang, J.; Du, G. The biology, function, and applications of exosomes in cancer. Acta Pharm. Sin. B, 2021, 11(9), 2783-2797.
[http://dx.doi.org/10.1016/j.apsb.2021.01.001] [PMID: 34589397]
[27]
Thakur, A.; Parra, D.C.; Motallebnejad, P.; Brocchi, M.; Chen, H.J. Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics. Bioact. Mater., 2021, 10, 281-294.
[http://dx.doi.org/10.1016/j.bioactmat.2021.08.029] [PMID: 34901546]
[28]
Bijnsdorp, I.V.; Geldof, A.A.; Lavaei, M. Exosomal ITAG3 interfacwith non-cancerous prostrate cell functions and is increased in urine exosomes of metastatic prostrate cancer patients. J. Extracell. Vesicles, 2013, 2.
[http://dx.doi.org/10.3402/jev.v2i0.22097]
[29]
Jiang, L.; Gu, Y.; Du, Y.; Liu, J. Exosomes: Diagnostic biomarkers and therapeutic delivery vehicles for cancer. Mol. Pharm., 2019, 16(8), 3333-3349.
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00409] [PMID: 31241965]
[30]
Yang, M.; Wu, S.Y. The advances and challenges in utilizing exosomes for delivering cancer therapeutics. Front. Pharmacol., 2018, 9, 735.
[http://dx.doi.org/10.3389/fphar.2018.00735] [PMID: 30061829]
[31]
Kibria, G.; Ramos, E.K.; Wan, Y.; Gius, D.R.; Liu, H. Exosomes as a drug delivery system in cancer therapy: Potential and challenges. Mol. Pharm., 2018, 15(9), 3625-3633.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00277] [PMID: 29771531]
[32]
Sinha, D.; Roy, S.; Saha, P.; Chatterjee, N.; Bishayee, A. Trends in research on exosomes in cancer progression and anticancer therapy. Cancers (Basel), 2021, 13(2), 1-31.
[http://dx.doi.org/10.3390/cancers13020326] [PMID: 33477340]
[33]
Vinik, Yaron.; Ortega, Francisco Gabriel. Mills, G.B.; Lu, Y.; Jarkowicz, M.; Halperin, S.; Aharoni, M.; Gutman, M.; Lev, S. Proteomic analy-sis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response. Sci. Adv., 2020, 6(40), eaba5714.
[34]
Tang, Y.; Zhang, Z.; Song, X.; Yu, M.; Niu, L.; Zhao, Y.; Wang, L.; Song, X.; Xie, L. Tumor-derived exosomal miR-620 as a diagnostic bi-omarker in non-small-cell lung cancer. J. Oncol., 2020, 2020, 6691211.
[http://dx.doi.org/10.1155/2020/6691211] [PMID: 33343663]
[35]
Shao, J.; Zaro, J.; Shen, Y. Advances in exosome-based drug delivery and tumor targeting: From tissue distribution to intracellular fate. Int. J. Nanomedicine, 2020, 15, 9355-9371.
[http://dx.doi.org/10.2147/IJN.S281890] [PMID: 33262592]
[36]
Diego de Miguel, P.; Martinez, A.R.; Palamo, A.O.; Mayte, D.U.J.L.G.P.; Remacho, A.R.; Hernandez, J.E.; Jose, A.L.A.; Francisco, G.O.S.; Serrano, M.J. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal can-cer patients. Sci. Rep., 2020, 10(1), 3974.
[http://dx.doi.org/10.1038/s41598-020-60212-1]
[37]
Wang, Z.; Chen, J.Q.; Liu, J.L.; Tian, L. Exosomes in tumor microenvironment: Novel transporters and biomarkers. J. Transl. Med., 2016, 14(1), 297.
[http://dx.doi.org/10.1186/s12967-016-1056-9] [PMID: 27756426]
[38]
Kaity, H. A review of exosomes and their role in the tumor microenvironment and host-“Tumor Macroenvironment”. J. Immunol. Sci., 2019, 3(1), 4-8.
[39]
Yang, L.; Huang, X.; Guo, H.; Wang, L.; Yang, W.; Wu, W.; Jing, D.; Shao, Z. Exosomes as efficient nanocarriers in osteosarcoma: Biological functions and potential clinical applications. Front.cell Dev. Bio., 2021, 9(737314), 1-14.
[40]
Patrick Santos and Fausto Almeida Exxosome –Based vaccines; History, Current state, and clinical trials. Front. Immunol., 2021, 12(711565), 1-15.
[41]
Dai, J.; Su, Y.; Zhong, S.; Cong, L.; Liu, B.; Yang, J.; Tao, Y.; He, Z.; Chen, C.; Jiang, Y. Exosomes: Key players in cancer and potential ther-apeutic strategy. Signal Transduct. Target. Ther., 2020, 5(1), 145.
[http://dx.doi.org/10.1038/s41392-020-00261-0]
[42]
Hussain, Z.; Rahim, M.A.; Jan, N.; Shah, H.; Rawas-Qalaji, M.; Khan, S.; Sohail, M.; Thu, H.E.; Ramli, N.A.; Sarfraz, R.M.; Abourehab, M.A.S. Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internaliza-tion and anticancer efficacy. J. Control. Release, 2021, 335, 130-157.
[http://dx.doi.org/10.1016/j.jconrel.2021.05.018] [PMID: 34015400]
[43]
Bagherifar, R.; Kiaie, S.H.; Hatami, Z.; Ahmadi, A.; Sadeghnejad, A.; Baradaran, B.; Jafari, R.; Javadzadeh, Y. Nanoparticle-mediated syner-gistic chemoimmunotherapy for tailoring cancer therapy: Recent advances and perspectives. J. Nanobiotechnology, 2021, 19(1), 110.
[http://dx.doi.org/10.1186/s12951-021-00861-0] [PMID: 33865432]
[44]
Mitchell, J. P. Exosomes in cancer immunology. 100.,
[45]
Chen, G.; Huang, A.C.; Zhang, W.; Zhang, G.; Wu, M.; Xu, W.; Yu, Z.; Yang, G.; Wang, B.; Sun, H.; Xia, F.; Man, Q.; Zhong, W.; Antelo, L.F.; Wu, B.; Xiong, X.; Liu, X.; Guan, L.; Li, T.; Liu, S.; Yang, R.; Lu, Y.; Dong, L.; McGettigan, S.; Somasundaram, R.; Radhakrishnan, R.; Mills, G.; Lu, Y.; Kim, J.; Chen, Y.H.; Dong, H.; Zhao, Y.; Karakousis, G.C.; Mitchell, T.C.; Schuchter, L.M.; Herlyn, M.; Wherry, E.J.; Xu, X.; Guo, W. Exosomal PD-L1 contributes to immunosupression and is associated with anti-PD-1 response. Nature, 2018, 560(7718), 382-386.
[http://dx.doi.org/10.1038/s41586-018-0392-8]
[46]
Mu, W.; Chu, Q.; Liu, Y.; Zhang, N. A review on nano-based drug delivery system for cancer chemoimmunotherapy. Nano-Micro Lett., 2020, 12(1), 142.
[http://dx.doi.org/10.1007/s40820-020-00482-6] [PMID: 34138136]
[47]
Xu, Z.; Zeng, S.; Gong, Z.; Yan, Y. Exosome-based immunotherapy: A promising approach for cancer treatment. Mol. Cancer, 2020, 19(1), 160.
[48]
Yin, Z.; Yu, M.; Ma, T.; Zhang, C.; Huang, S.; Karimzadeh, M.R.; Momtazi-Borojeni, A.A.; Chen, S. Mechanisms underlying low-clinical response to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: A key role of exosomal PD- L1. J. Immunother. Cancer, 2021, 9(1), e001698.
[http://dx.doi.org/10.1136/jitc-2020-001698]
[49]
Pathak, R.; De Lima Lopes, G.; Yu, H.; Aryal, M.R.; Ji, W.; Frumento, K.S.; Wallis, C.J.D.; Klaassen, Z.; Park, H.S.; Goldberg, S.B. Compara-tive efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of random-ized trials. Cancer, 2021, 127(5), 709-719.
[http://dx.doi.org/10.1002/cncr.33269] [PMID: 33119177]
[50]
Li, A.; Zhao, Y.; Li, Y.; Jiang, L.; Gu, Y.; Liu, J. Cell-derived biomimetic nanocarriers for targeted cancer therapy: Cell membranes and extra-cellular vesicles. Drug Deliv., 2021, 28(1), 1237-1255.
[http://dx.doi.org/10.1080/10717544.2021.1938757] [PMID: 34142930]
[51]
Storm, G.; ten Kate, M.T.; Working, P.K.; Bakker-Woudenberg, I.A. Doxorubicin on bacterial phagocyte entrapped blood system in sterically capacity stabilized of the liposomes: Mononuclear effects clearance. Clin. Cancer Res., 1998, 3, 111-115.
[PMID: 9516959]
[52]
Yang, Y-C.; Liu, G-J.; Yuan, D-F.; Li, C-Q.; Xue, M.; Chen, L-J. Influence of exosome-derived miR-21 on chemotherapy resistance of esophageal cancer. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(4), 1513-1519.
[53]
Alharbi, M.; Zuniga, F.; Elfeky, O.; Guanzon, D.; Lal, A.; Rice, G.E.; Perrin, L.; Hooper, J.; Salomon, C. The potential role of miRNAs and exosomes in chemotherapy in ovarian cancer. Endocr. Relat. Cancer, 2018, 25(12), R663-R685.
[54]
Yong, T.; Zhang, X.; Bie, N.; Zhang, H.; Zhang, X.; Li, F.; Hakeem, A.; Hu, J.; Gan, L.; Santos, H.A.; Yang, X. Tumor exosome-based nano-particles are efficient drug carriers for chemotherapy. Nat. Commun., 2019, 10(1), 3838.
[http://dx.doi.org/10.1038/s41467-019-11718-4] [PMID: 31444335]
[55]
Zhao, J.; Ma, S.; Xu, Y.; Si, X.; Yao, H.; Huang, Z.; Zhang, Y.; Yu, H.; Tang, Z.; Song, W.; Chen, X. In situ activation of STING pathway with polymeric SN38 for cancer chemoimmunotherapy. Biomaterials, 2021, 268, 120542.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120542] [PMID: 33249316]
[56]
Pitt, J.M.; Andre, F.; Amigorena, S.; Soria, J-C.; Eggermont, A.; Kroemer, G.; Zitvogel, L. Dendritic cell - derived exosomes for cancer thera-py. J. Clin. Invest., 2016, 126, 1224-1232.
[57]
Tian, H.; Li, W. Dendritic cell-derived exosomes for cancer immunotherapy: Hope and challenges. Ann. Transl. Med., 2017, 5(10), 221.
[58]
Wang, Y.; Zhang, Y.; Cai, G.; Li, Q. Exosomes as actively targeted nanocarriers for cancer therapy. Int. J. Nanomedicine, 2020, 15, 4257-4273.
[59]
Herrmann, I.K.; Wood, M.J.A.; Fuhrmann, G. Extracellular vesicles as a next-generation drug delivery platform. Nat. Nanotechnol., 2021, 16(7), 748-759.
[http://dx.doi.org/10.1038/s41565-021-00931-2] [PMID: 34211166]

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