Exosome as a Natural Gene Delivery Vector for Cancer Treatment

Author(s): Prasad Pofali, Adrita Mondal, Vaishali Londhe*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 11 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier.

Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article.

Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes.

Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects.

Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.

Keywords: Exosome, immunologically inert, biocompatible, gene therapy, cancer, nanocarrier.

[1]
Qin, J.; Xu, Q. Functions and application of exosomes. Acta Pol. Pharm., 2014, 71(4), 537-543.
[PMID: 25272880]
[2]
Caby, M.P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol., 2005, 17(7), 879-887.
[http://dx.doi.org/10.1093/intimm/dxh267] [PMID: 15908444]
[3]
Ha, D.; Yang, N.; Nadithe, V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm. Sin. B, 2016, 6(4), 287-296.
[http://dx.doi.org/10.1016/j.apsb.2016.02.001] [PMID: 27471669]
[4]
van den Boorn, J.G.; Schlee, M.; Coch, C.; Hartmann, G. SiRNA delivery with exosome nanoparticles. Nat. Biotechnol., 2011, 29(4), 325-326.
[http://dx.doi.org/10.1038/nbt.1830] [PMID: 21478846]
[5]
Yu, L.L.; Zhu, J.; Liu, J.X.; Jiang, F.; Ni, W.K.; Qu, L.S.; Ni, R.Z.; Lu, C.H.; Xiao, M.B. A comparison of traditional and novel methods for the separation of exosomes from human samples. BioMed Res. Int., 2018, 2018, 3634563.
[http://dx.doi.org/10.1155/2018/3634563] [PMID: 30148165]
[6]
Liang, L.G.; Kong, M.Q.; Zhou, S.; Sheng, Y.F.; Wang, P.; Yu, T.; Inci, F.; Kuo, W.P.; Li, L.J.; Demirci, U.; Wang, S. An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer. Sci. Rep., 2017, 7, 46224.
[http://dx.doi.org/10.1038/srep46224] [PMID: 28436447]
[7]
Alvarez, M.L.; Khosroheidari, M.; Kanchi Ravi, R.; DiStefano, J.K. Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers. Kidney Int., 2012, 82(9), 1024-1032.
[http://dx.doi.org/10.1038/ki.2012.256] [PMID: 22785172]
[8]
Sharma, P.; Ludwig, S.; Muller, L.; Hong, C.S.; Kirkwood, J.M.; Ferrone, S.; Whiteside, T.L. Immunoaffinity-based isolation of melanoma cell-derived exosomes from plasma of patients with melanoma. J. Extracell. Vesicles, 2018, 7(1), 1435138.
[http://dx.doi.org/10.1080/20013078.2018.1435138] [PMID: 29511460]
[9]
Contreras-Naranjo, J.C.; Wu, H.J.; Ugaz, V.M. Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip, 2017, 17(21), 3558-3577.
[http://dx.doi.org/10.1039/C7LC00592J] [PMID: 28832692]
[10]
Blackadar, C.B. Historical review of the causes of cancer. World J. Clin. Oncol., 2016, 7(1), 54-86.
[http://dx.doi.org/10.5306/wjco.v7.i1.54] [PMID: 26862491]
[11]
Zhang, H.; Chen, J. Current status and future directions of cancer immunotherapy. J. Cancer, 2018, 9(10), 1773-1781.
[http://dx.doi.org/10.7150/jca.24577] [PMID: 29805703]
[12]
Cross, D.; Burmester, J.K. Gene therapy for cancer treatment: past, present and future. Clin. Med. Res., 2006, 4(3), 218-227.
[http://dx.doi.org/10.3121/cmr.4.3.218] [PMID: 16988102]
[13]
Cristiano, R.J. Viral and non-viral vectors for cancer gene therapy. Anticancer Res., 1998, 18(5A), 3241-3245.
[PMID: 9858889]
[14]
Wirth, T.; Ylä-Herttuala, S. Gene therapy used in cancer treatment. Biomedicines, 2014, 2(2), 149-162.
[http://dx.doi.org/10.3390/biomedicines2020149] [PMID: 28548065]
[15]
Coura, R.D.S.; Nardi, N.B. A role for adeno-associated viral vectors in gene therapy. Genet. Mol. Biol., 2008, 31(1), 1-11.
[http://dx.doi.org/10.1590/S1415-47572008000100001]
[16]
Vannucci, L.; Lai, M.; Chiuppesi, F.; Ceccherini-Nelli, L.; Pistello, M. Viral vectors: a look back and ahead on gene transfer technology. New Microbiol., 2013, 36(1), 1-22.
[PMID: 23435812]
[17]
Goswami, R.; Subramanian, G.; Silayeva, L.; Newkirk, I.; Doctor, D.; Chawla, K.; Chattopadhyay, S.; Chandra, D.; Chilukuri, N.; Betapudi, V. Gene therapy leaves a vicious cycle. Front. Oncol., 2019, 9, 297.
[http://dx.doi.org/10.3389/fonc.2019.00297] [PMID: 31069169]
[18]
Thomas, C.E.; Ehrhardt, A.; Kay, M.A. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet., 2003, 4(5), 346-358.
[http://dx.doi.org/10.1038/nrg1066] [PMID: 12728277]
[19]
Al-Dosari, M.S.; Gao, X. Nonviral gene delivery: principle, limitations, and recent progress. AAPS J., 2009, 11(4), 671-681.
[http://dx.doi.org/10.1208/s12248-009-9143-y] [PMID: 19834816]
[20]
Dizaj, S.M.; Jafari, S.; Khosroushahi, A.Y. A sight on the current nanoparticle-based gene delivery vectors. Nanoscale Res. Lett., 2014, 9(1), 252.
[http://dx.doi.org/10.1186/1556-276X-9-252] [PMID: 24936161]
[21]
Ramamoorth, M.; Narvekar, A. Non viral vectors in gene therapy- an overview. J. Clin. Diagn. Res., 2015, 9(1), GE01-GE06.
[http://dx.doi.org/10.7860/JCDR/2015/10443.5394] [PMID: 25738007]
[22]
Mellott, A.J.; Forrest, M.L.; Detamore, M.S. Physical non-viral gene delivery methods for tissue engineering. Ann. Biomed. Eng., 2013, 41(3), 446-468.
[http://dx.doi.org/10.1007/s10439-012-0678-1] [PMID: 23099792]
[23]
Cronin, M.; Stanton, R.M.; Francis, K.P.; Tangney, M. Bacterial vectors for imaging and cancer gene therapy: a review. Cancer Gene Ther., 2012, 19(11), 731-740.
[http://dx.doi.org/10.1038/cgt.2012.59] [PMID: 22996740]
[24]
Baban, C.K.; Cronin, M.; O’Hanlon, D.; O’Sullivan, G.C.; Tangney, M. Bacteria as vectors for gene therapy of cancer. Bioeng. Bugs, 2010, 1(6), 385-394.
[http://dx.doi.org/10.4161/bbug.1.6.13146] [PMID: 21468205]
[25]
Zhou, Y.; Zhou, G.; Tian, C.; Jiang, W.; Jin, L.; Zhang, C.; Chen, X. Exosome-mediated small RNA delivery for gene therapy. Wiley Interdiscip. Rev. RNA, 2016, 7(6), 758-771.
[http://dx.doi.org/10.1002/wrna.1363] [PMID: 27196002]
[26]
Rezaie, J.; Ajezi, S.; Avci, Ç.B.; Karimipour, M.; Geranmayeh, M.H.; Nourazarian, A.; Sokullu, E.; Rezabakhsh, A.; Rahbarghazi, R. Exosomes and their application in biomedical field: difficulties and advantages. Mol. Neurobiol., 2018, 55(4), 3372-3393.
[http://dx.doi.org/10.1007/s12035-017-0582-7] [PMID: 28497202]
[27]
Gao, D.; Jiang, L. Exosomes in cancer therapy: a novel experimental strategy. Am. J. Cancer Res., 2018, 8(11), 2165-2175.
[PMID: 30555736]
[28]
Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer, 2012, 12(4), 265-277.
[http://dx.doi.org/10.1038/nrc3258] [PMID: 22437871]
[29]
Zeelenberg, I.S.; Ostrowski, M.; Krumeich, S.; Bobrie, A.; Jancic, C.; Boissonnas, A.; Delcayre, A.; Le Pecq, J.B.; Combadière, B.; Amigorena, S.; Théry, C. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res., 2008, 68(4), 1228-1235.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-3163] [PMID: 18281500]
[30]
De Toro, J.; Herschlik, L.; Waldner, C.; Mongini, C. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front. Immunol., 2015, 6, 203.
[http://dx.doi.org/10.3389/fimmu.2015.00203] [PMID: 25999947]
[31]
Huang, T.; Deng, C.X. Current progresses of exosomes as cancer diagnostic and prognostic biomarkers. Int. J. Biol. Sci., 2019, 15(1), 1-11.
[http://dx.doi.org/10.7150/ijbs.27796] [PMID: 30662342]
[32]
Sun, D.; Zhuang, X.; Xiang, X.; Liu, Y.; Zhang, S.; Liu, C.; Barnes, S.; Grizzle, W.; Miller, D.; Zhang, H.G. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol. Ther., 2010, 18(9), 1606-1614.
[http://dx.doi.org/10.1038/mt.2010.105] [PMID: 20571541]
[33]
Didiot, M.C.; Hall, L.M.; Coles, A.H.; Haraszti, R.A.; Godinho, B.M.; Chase, K.; Sapp, E.; Ly, S.; Alterman, J.F.; Hassler, M.R.; Echeverria, D.; Raj, L.; Morrissey, D.V.; DiFiglia, M.; Aronin, N.; Khvorova, A. Exosome-mediated delivery of hydrophobically modified siRNA for Huntingtin mRNA silencing. Mol. Ther., 2016, 24(10), 1836-1847.
[http://dx.doi.org/10.1038/mt.2016.126] [PMID: 27506293]
[34]
Li, S.P.; Lin, Z.X.; Jiang, X.Y.; Yu, X.Y. Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacol. Sin., 2018, 39(4), 542-551.
[http://dx.doi.org/10.1038/aps.2017.178] [PMID: 29417947]
[35]
Faruqu, F.N.; Xu, L.; Al-Jamal, K.T. Preparation of Exosomes for siRNA Delivery to Cancer Cells. 2008. (142), e58814.
[http://dx.doi.org/10.3791/58814]
[36]
Akao, Y.; Nakagawa, Y.; Hirata, I.; Iio, A.; Itoh, T.; Kojima, K.; Nakashima, R.; Kitade, Y.; Naoe, T. Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther., 2010, 17(6), 398-408.
[http://dx.doi.org/10.1038/cgt.2009.88] [PMID: 20094072]
[37]
Zhang, Y.; Liu, D.; Chen, X.; Li, J.; Li, L.; Bian, Z.; Sun, F.; Lu, J.; Yin, Y.; Cai, X.; Sun, Q.; Wang, K.; Ba, Y.; Wang, Q.; Wang, D.; Yang, J.; Liu, P.; Xu, T.; Yan, Q.; Zhang, J.; Zen, K.; Zhang, C.Y. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell, 2010, 39(1), 133-144.
[http://dx.doi.org/10.1016/j.molcel.2010.06.010] [PMID: 20603081]
[38]
Lamichhane, T.N.; Raiker, R.S.; Jay, S.M. Exogenous DNA loading into extracellular vesicles via electroporation is size-dependent and enables limited gene delivery. Mol. Pharm., 2015, 12(10), 3650-3657.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00364] [PMID: 26376343]
[39]
Lamichhane, T.N.; Jeyaram, A.; Patel, D.B.; Parajuli, B.; Livingston, N.K.; Arumugasaamy, N.; Schardt, J.S.; Jay, S.M. Oncogene knockdown via active loading of small RNAs into extracellular vesicles by sonication. Cell. Mol. Bioeng., 2016, 9(3), 315-324.
[http://dx.doi.org/10.1007/s12195-016-0457-4] [PMID: 27800035]
[40]
Antimisiaris, S.G.; Mourtas, S.; Marazioti, A. Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics, 2018, 10(4), 218.
[http://dx.doi.org/10.3390/pharmaceutics10040218] [PMID: 30404188]
[41]
Wang, T.; Shigdar, S.; Shamaileh, H.A.; Gantier, M.P.; Yin, W.; Xiang, D.; Wang, L.; Zhou, S.F.; Hou, Y.; Wang, P.; Zhang, W.; Pu, C.; Duan, W. Challenges and opportunities for siRNA-based cancer treatment. Cancer Lett., 2017, 387, 77-83.
[http://dx.doi.org/10.1016/j.canlet.2016.03.045] [PMID: 27045474]
[42]
Kooijmans, S.A.A.; Stremersch, S.; Braeckmans, K.; de Smedt, S.C.; Hendrix, A.; Wood, M.J.A.; Schiffelers, R.M.; Raemdonck, K.; Vader, P. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J. Control. Release, 2013, 172(1), 229-238.
[http://dx.doi.org/10.1016/j.jconrel.2013.08.014] [PMID: 23994516]
[43]
Lu, M.; Xing, H.; Xun, Z.; Yang, T.; Ding, P.; Cai, C.; Wang, D.; Zhao, X. Exosome-based small RNA delivery: Progress and prospects. Asian J. Pharm. Sci., 2018, 13(1), 1-11.
[44]
Li, Z.; Wang, H.; Yin, H.; Bennett, C.; Zhang, H.G.; Guo, P. Arrowtail RNA for ligand display on ginger exosome-like nanovesicles to systemic deliver siRNA for cancer suppression. Sci. Rep., 2018, 8(1), 14644.
[http://dx.doi.org/10.1038/s41598-018-32953-7] [PMID: 30279553]
[45]
Yang, T.; Fogarty, B.; LaForge, B.; Aziz, S.; Pham, T.; Lai, L.; Bai, S. Delivery of small interfering RNA to inhibit vascular endothelial growth factor in zebrafish using natural brain endothelia cell-secreted exosome nanovesicles for the treatment of brain cancer. AAPS J., 2017, 19(2), 475-486.
[http://dx.doi.org/10.1208/s12248-016-0015-y] [PMID: 27882487]
[46]
Husmann, K.; Ducommun, P.; Sabile, A.A.; Pedersen, E.M.; Born, W.; Fuchs, B. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells. Biochem. Biophys. Res. Commun., 2015, 464(4), 1222-1227.
[http://dx.doi.org/10.1016/j.bbrc.2015.07.108] [PMID: 26210452]
[47]
Zhang, H.; Wang, Y.; Bai, M.; Wang, J.; Zhu, K.; Liu, R.; Ge, S.; Li, J.; Ning, T.; Deng, T.; Fan, Q.; Li, H.; Sun, W.; Ying, G.; Ba, Y. Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Sci., 2018, 109(3), 629-641.
[http://dx.doi.org/10.1111/cas.13488] [PMID: 29285843]
[48]
Kamerkar, S.; LeBleu, V.S.; Sugimoto, H.; Yang, S.; Ruivo, C.F.; Melo, S.A.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature, 2017, 546(7659), 498-503.
[http://dx.doi.org/10.1038/nature22341] [PMID: 28607485]
[49]
Allenson, K.; Castillo, J.; San Lucas, F.A.; Scelo, G.; Kim, D.U.; Bernard, V.; Davis, G.; Kumar, T.; Katz, M.; Overman, M.J.; Foretova, L.; Fabianova, E.; Holcatova, I.; Janout, V.; Meric-Bernstam, F.; Gascoyne, P.; Wistuba, I.; Varadhachary, G.; Brennan, P.; Hanash, S.; Li, D.; Maitra, A.; Alvarez, H. High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. Ann. Oncol., 2017, 28(4), 741-747.
[http://dx.doi.org/10.1093/annonc/mdx004] [PMID: 28104621]
[50]
Wahid, F.; Shehzad, A.; Khan, T.; Kim, Y.Y. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim. Biophys. Acta, 2010, 1803(11), 1231-1243.
[http://dx.doi.org/10.1016/j.bbamcr.2010.06.013] [PMID: 20619301]
[51]
Kaboli, P.J.; Rahmat, A.; Ismail, P.; Ling, K.H. MicroRNA-based therapy and breast cancer: A comprehensive review of novel therapeutic strategies from diagnosis to treatment. Pharmacol. Res., 2015, 97, 104-121.
[http://dx.doi.org/10.1016/j.phrs.2015.04.015] [PMID: 25958353]
[52]
Bach, D.H.; Hong, J.Y.; Park, H.J.; Lee, S.K. The role of exosomes and miRNAs in drug-resistance of cancer cells. Int. J. Cancer, 2017, 141(2), 220-230.
[http://dx.doi.org/10.1002/ijc.30669] [PMID: 28240776]
[53]
Lowry, M.C.; Gallagher, W.M.; O’Driscoll, L. The role of exosomes in breast cancer. Clin. Chem., 2015, 61(12), 1457-1465.
[http://dx.doi.org/10.1373/clinchem.2015.240028] [PMID: 26467503]
[54]
Miller, T.E.; Ghoshal, K.; Ramaswamy, B.; Roy, S.; Datta, J.; Shapiro, C.L.; Jacob, S.; Majumder, S. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem., 2008, 283(44), 29897-29903.
[http://dx.doi.org/10.1074/jbc.M804612200] [PMID: 18708351]
[55]
Kovalchuk, O.; Filkowski, J.; Meservy, J.; Ilnytskyy, Y.; Tryndyak, V.P.; Chekhun, V.F.; Pogribny, I.P. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol. Cancer Ther., 2008, 7(7), 2152-2159.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0021] [PMID: 18645025]
[56]
Xin, F.; Li, M.; Balch, C.; Thomson, M.; Fan, M.; Liu, Y.; Hammond, S.M.; Kim, S.; Nephew, K.P. Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance. Bioinformatics, 2009, 25(4), 430-434.
[http://dx.doi.org/10.1093/bioinformatics/btn646] [PMID: 19091772]
[57]
Pan, Y.Z.; Morris, M.E.; Yu, A.M. MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol. Pharmacol., 2009, 75(6), 1374-1379.
[http://dx.doi.org/10.1124/mol.108.054163] [PMID: 19270061]
[58]
Chen, G.Q.; Zhao, Z.W.; Zhou, H.Y.; Liu, Y.J.; Yang, H.J. Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin. Med. Oncol., 2010, 27(2), 406-415.
[http://dx.doi.org/10.1007/s12032-009-9225-9] [PMID: 19412672]
[59]
Sorrentino, A.; Liu, C.G.; Addario, A.; Peschle, C.; Scambia, G.; Ferlini, C. Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol. Oncol., 2008, 111(3), 478-486.
[http://dx.doi.org/10.1016/j.ygyno.2008.08.017] [PMID: 18823650]
[60]
Zhu, H.; Wu, H.; Liu, X.; Evans, B.R.; Medina, D.J.; Liu, C.G.; Yang, J.M. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol., 2008, 76(5), 582-588.
[http://dx.doi.org/10.1016/j.bcp.2008.06.007] [PMID: 18619946]
[61]
Blower, P.E.; Chung, J.H.; Verducci, J.S.; Lin, S.; Park, J.K.; Dai, Z.; Liu, C.G.; Schmittgen, T.D.; Reinhold, W.C.; Croce, C.M.; Weinstein, J.N.; Sadee, W. MicroRNAs modulate the chemosensitivity of tumor cells. Mol. Cancer Ther., 2008, 7(1), 1-9.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0573] [PMID: 18187804]
[62]
Döhner, H.; Fischer, K.; Bentz, M.; Hansen, K.; Benner, A.; Cabot, G.; Diehl, D.; Schlenk, R.; Coy, J.; Stilgenbauer, S. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood, 1995, 85(6), 1580-1589.
[http://dx.doi.org/10.1182/blood.V85.6.1580.bloodjournal8561580] [PMID: 7888675]
[63]
Zhu, W.; Shan, X.; Wang, T.; Shu, Y.; Liu, P. miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int. J. Cancer, 2010, 127(11), 2520-2529.
[http://dx.doi.org/10.1002/ijc.25260] [PMID: 20162574]
[64]
Ji, Q.; Hao, X.; Meng, Y.; Zhang, M.; Desano, J.; Fan, D.; Xu, L. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer, 2008, 8(1), 266.
[http://dx.doi.org/10.1186/1471-2407-8-266] [PMID: 18803879]
[65]
Xia, L.; Zhang, D.; Du, R.; Pan, Y.; Zhao, L.; Sun, S.; Hong, L.; Liu, J.; Fan, D. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int. J. Cancer, 2008, 123(2), 372-379.
[http://dx.doi.org/10.1002/ijc.23501] [PMID: 18449891]
[66]
Fang, Y.; Shen, H.; Li, H.; Cao, Y.; Qin, R.; Long, L.; Zhu, X.; Xie, C.; Xu, W. miR-106a confers cisplatin resistance by regulating PTEN/Akt pathway in gastric cancer cells. Acta Biochim. Biophys. Sin. (Shanghai), 2013, 45(11), 963-972.
[http://dx.doi.org/10.1093/abbs/gmt106] [PMID: 24108762]
[67]
Fujita, Y.; Kojima, K.; Hamada, N.; Ohhashi, R.; Akao, Y.; Nozawa, Y.; Deguchi, T.; Ito, M. Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem. Biophys. Res. Commun., 2008, 377(1), 114-119.
[http://dx.doi.org/10.1016/j.bbrc.2008.09.086] [PMID: 18834855]
[68]
Nakajima, G.; Hayashi, K.; Xi, Y.; Kudo, K.; Uchida, K.; Takasaki, K.; Yamamoto, M.; Ju, J. Non-coding MicroRNAs hsa-let-7g and hsa-miR-181b are Associated with Chemoresponse to S-1 in Colon Cancer. Cancer Genomics Proteomics, 2006, 3(5), 317-324.
[PMID: 18172508]
[69]
Pegtel, D.M.; Cosmopoulos, K.; Thorley-Lawson, D.A.; van Eijndhoven, M.A.; Hopmans, E.S.; Lindenberg, J.L.; de Gruijl, T.D.; Würdinger, T.; Middeldorp, J.M. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA, 2010, 107(14), 6328-6333.
[http://dx.doi.org/10.1073/pnas.0914843107] [PMID: 20304794]
[70]
Zhan, T.; Rindtorff, N.; Betge, J.; Ebert, M.P.; Boutros, M. CRISPR/Cas9 for cancer research and therapy. Seminars in cancer biology; Academic Press, 2018.
[71]
Sander, J.D.; Joung, J.K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol., 2014, 32(4), 347-355.
[http://dx.doi.org/10.1038/nbt.2842] [PMID: 24584096]
[72]
Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J.A.; Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012, 337(6096), 816-821.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[73]
Martinez-Lage, M.; Puig-Serra, P.; Menendez, P.; Torres-Ruiz, R.; Rodriguez-Perales, S. CRISPR/Cas9 for cancer therapy: hopes and challenges. Biomedicines, 2018, 6(4), 105.
[http://dx.doi.org/10.3390/biomedicines6040105] [PMID: 30424477]
[74]
Kim, S.M.; Yang, Y.; Oh, S.J.; Hong, Y.; Seo, M.; Jang, M. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J. Control. Release, 2017, 266, 8-16.
[http://dx.doi.org/10.1016/j.jconrel.2017.09.013] [PMID: 28916446]
[76]
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]
[77]
Yamashita, T.; Takahashi, Y.; Takakura, Y. Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application. Biol. Pharm. Bull., 2018, 41(6), 835-842.
[http://dx.doi.org/10.1248/bpb.b18-00133] [PMID: 29863072]
[78]
Zhou, H.; Yuen, P.S.; Pisitkun, T.; Gonzales, P.A.; Yasuda, H.; Dear, J.W.; Gross, P.; Knepper, M.A.; Star, R.A. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int., 2006, 69(8), 1471-1476.
[http://dx.doi.org/10.1038/sj.ki.5000273] [PMID: 16501490]
[79]
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]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 11
Year: 2020
Published on: 02 December, 2020
Page: [821 - 830]
Pages: 10
DOI: 10.2174/1568009620666200924154149
Price: $65

Article Metrics

PDF: 47
HTML: 2