Generic placeholder image

Current Analytical Chemistry

Editor-in-Chief

ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

Research Article

Combination of ZnO Nanoparticle with Marine Sponge Derived Dipeptide for Enhanced Anticancer Efficacy in Liver Cancer Cells and their Toxicity Evaluation on Embryonic Zebrafish

Author(s): Gayathri Karanam, Arumugam Madan Kumar*, Chinmai Sriamulya Yerukalapudi, Nagabhishek Sirpu Natesh, Rajender Boddula and Ramyakrishna Pothu

Volume 17, Issue 5, 2021

Published on: 06 January, 2020

Page: [677 - 688] Pages: 12

DOI: 10.2174/1573411016666200106101109

Price: $65

Abstract

Background: Nanomaterials-based cancer therapy plays a significant role in increasing the therapeutic efficiency of anticancer drugs, reducing side effects and targeted delivery of the drug payloads. The present study was aimed to enhance the anticancer effect of a novel dipeptide isolated from marine sponge-associated Bacillus pumilus AMK1 by formulating with Zinc oxide (ZnO) nanoparticles for the effective treatment against HepG2 liver cancer cells.

Methods: ZnO nanoparticles were synthesized by chemical method and size of the nanoparticle was characterized by Scanning electron microscope, X-Ray diffraction and Fourier-transform infrared spectroscopy. Furthermore, ZnO nanoparticles were conjugated with the isolated dipeptide and evaluated for anticancer activity. In addition, distinct morphological changes were observed by performing apoptotic staining methods such as propidium iodide staining and acridine orange/ ethidium bromide staining. Furthermore, embryotoxic and teratogenic effects of conjugated dipeptide on the development of zebrafish embryo were investigated in this study.

Results: It was observed that conjugated dipeptide showed enhanced cytotoxicity against HepG2 liver cancer cells without any toxic effect on normal liver cells. ZnO with dipeptide showed significant higher apoptosis of liver cancer cells, with around 19% in early apoptosis and 53% in late apoptosis stage. The obtained results suggest that ZnO nanoparticle conjugated dipeptide initiated cytotoxicity through apoptotic death in HepG2 cells. The embryotoxic studies in zebrafish embryos revealed the LC50 197.0 μg/mL. These findings suggest that conjugated dipeptide affected the development of zebrafish embryos only at relatively higher concentrations.

Conclusion: The experimental results demonstrate that ZnO nanoparticle conjugated dipeptide has the potential to improve anticancer efficacy against liver cancer cells by inducing apoptosis in cancer cells without any effect on normal liver cells.

Keywords: Anticancer, apoptosis, dipeptide, marine sponge, zebrafish embryotoxicity, ZnO nanoparticles.

Graphical Abstract
[1]
Singh, R.; Lillard, J.W. Jr Nanoparticle-based targeted drug delivery. Exp. Mol. Pathol., 2009, 86(3), 215-223.
[http://dx.doi.org/10.1016/j.yexmp.2008.12.004] [PMID: 19186176]
[2]
De Jong, W.H.; Borm, P.J. Drug delivery and nanoparticles:applications and hazards. Int. J. Nanomedicine, 2008, 3(2), 133-149.
[http://dx.doi.org/10.2147/IJN.S596] [PMID: 18686775]
[3]
Din, F.U.; Aman, W.; Ullah, I.; Qureshi, O.S.; Mustapha, O.; Shafique, S.; Zeb, A. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int. J. Nanomedicine, 2017, 12, 7291-7309.
[http://dx.doi.org/10.2147/IJN.S146315] [PMID: 29042776]
[4]
Weissig, V.; Pettinger, T.K.; Murdock, N. Nanopharmaceuticals (part 1): Products on the market. Int. J. Nanomedicine, 2014, 9, 4357-4373.
[http://dx.doi.org/10.2147/IJN.S46900] [PMID: 25258527]
[5]
Xin, Y.; Yin, M.; Zhao, L.; Meng, F.; Luo, L. Recent progress on nanoparticle-based drug delivery systems for cancer therapy. Cancer Biol. Med., 2017, 14(3), 228-241.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0052] [PMID: 28884040]
[6]
Zhang, Y.; Nayak, T.R.; Hong, H.; Cai, W. Biomedical applications of zinc oxide nanomaterials. Curr. Mol. Med., 2013, 13(10), 1633-1645.
[http://dx.doi.org/10.2174/1566524013666131111130058] [PMID: 24206130]
[7]
Rasmussen, J.W.; Martinez, E.; Louka, P.; Wingett, D.G. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opin. Drug Deliv., 2010, 7(9), 1063-1077.
[http://dx.doi.org/10.1517/17425247.2010.502560] [PMID: 20716019]
[8]
Hanley, C.; Layne, J.; Punnoose, A.; Reddy, K.M.; Coombs, I.; Coombs, A.; Feris, K.; Wingett, D. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles. Nanotechnology, 2008, 19(29)295103
[http://dx.doi.org/10.1088/0957-4484/19/29/295103] [PMID: 18836572]
[9]
Ramsey, S.D.; Veenstra, D.; Tunis, S.R.; Garrison, L.; Crowley, J.J.; Baker, L.H. How comparative effectiveness research can help advance ‘personalized medicine’ in cancer treatment. Health Aff. (Millwood), 2011, 30(12), 2259-2268.
[http://dx.doi.org/10.1377/hlthaff.2010.0637] [PMID: 22147853]
[10]
Lee, Y.; Phat, C.; Hong, S.C. Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications. Peptides, 2017, 95, 94-105.
[http://dx.doi.org/10.1016/j.peptides.2017.06.002] [PMID: 28610952]
[11]
Karanam, G.; Arumugam, M.K.; Sirpu Natesh, N. Anticancer effect of marine sponge-associated bacillus pumilus AMK1 Derived Dipeptide Cyclo (-Pro-Tyr) in human liver cancer cell line through apoptosis and G2/M Phase Arrest. Int. J. Pept. Res. Ther., 2020, 26, 445-457.
[http://dx.doi.org/10.1007/s10989-019-09850-2]
[12]
Nowik, N.; Podlasz, P.; Jakimiuk, A.; Kasica, N.; Sienkiewicz, W.; Kaleczyc, J. Zebrafish: An animal model for research in veterinary medicine. Pol. J. Vet. Sci., 2015, 18(3), 663-674.
[http://dx.doi.org/10.1515/pjvs-2015-0086] [PMID: 26618602]
[13]
Blagosklonny, M.V. Teratogens as anti-cancer drugs. Cell Cycle, 2005, 4(11), 1518-1521.
[http://dx.doi.org/10.4161/cc.4.11.2208] [PMID: 16258270]
[14]
Zhu, L.; Zeng, W.; Li, Y. New insight into gas sensing property of ZnO nanorods and nanosheets. Mater. Lett., 2018, 228, 331-333.
[http://dx.doi.org/10.1016/j.matlet.2018.06.049]
[15]
Bai Aswathanarayan, J.; Rai Vittal, R.; Muddegowda, U. Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells. Artif. Cells Nanomed. Biotechnol., 2018, 46(7), 1444-1451.
[http://dx.doi.org/10.1080/21691401.2017.1373655] [PMID: 28884587]
[16]
Sirpu Natesh, N.; Arumugam, M.; Karanam, G. Apoptotic role of marine sponge symbiont Bacillus subtilis NMK17 through the activation of caspase-3 in human breast cancer cell line. Mol. Biol. Rep., 2018, 45(6), 2641-2651.
[http://dx.doi.org/10.1007/s11033-018-4434-y] [PMID: 30414102]
[17]
Nocker, A.; Cheung, C.Y.; Camper, A.K. Comparison of propidium monoazide with ethidium monoazide for differentiation of live vs. dead bacteria by selective removal of DNA from dead cells. J. Microbiol. Methods, 2006, 67(2), 310-320.
[http://dx.doi.org/10.1016/j.mimet.2006.04.015] [PMID: 16753236]
[18]
Truong, L.; Harper, S.L.; Tanguay, R.L. Evaluation of embryotoxicity using the zebrafish model. Methods Mol. Biol., 2011, 691, 271-279.
[http://dx.doi.org/10.1007/978-1-60761-849-2_16] [PMID: 20972759]
[19]
Dulay, R.M.; Kalaw, S.P.; Reyes, R.G.; Alfonso, N.F.; Eguchi, F. Teratogenic and toxic effects of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.) P. Karst. (higher Basidiomycetes), on zebrafish embryo as model. Int. J. Med. Mushrooms, 2012, 14(5), 507-512.
[http://dx.doi.org/10.1615/IntJMedMushr.v14.i5.90] [PMID: 23510220]
[20]
Levin, E.D.; Swain, H.A.; Donerly, S.; Linney, E. Developmental chlorpyrifos effects on hatchling zebrafish swimming behavior. Neurotoxicol. Teratol., 2004, 26(6), 719-723.
[http://dx.doi.org/10.1016/j.ntt.2004.06.013] [PMID: 15451035]
[21]
Nagel, R. DarT: The embryo test with the Zebrafish Danio rerio--a general model in ecotoxicology and toxicology. ALTEX 19 Suppl, 2002, 1, 38-48.
[22]
Sharma, D.; Rajput, J.; Kaith, B.S.; Kaur, M.; Sharma, S. Synthesis of ZnO nanoparticles and study of their antibacterial and antifungal properties. Thin Solid Films, 2010, 519, 1224.
[http://dx.doi.org/10.1016/j.tsf.2010.08.073]
[23]
Sayari, A.; El Mir, L.; Bardeleben, H.J.V. Structural, EPR and optical properties of Zn0.75TM0.25O (TM, Mn, Fe, Co, Ni) aerogel nanoparticles. Eur. Phys. J. Appl. Phys., 2014, 67, 10401.
[http://dx.doi.org/10.1051/epjap/2014140074]
[24]
Aditya, A.; Chattopadhyay, S.; Gupta, N.; Alam, S.; Veedu, A.P.; Pal, M.; Singh, A.; Santhiya, D.; Ansari, K.M.; Ganguli, M. ZnO Nanoparticles Modified with an Amphipathic Peptide Show Improved Photoprotection in Skin. ACS Appl. Mater. Interfaces, 2019, 11(1), 56-72.
[http://dx.doi.org/10.1021/acsami.8b08431] [PMID: 30507150]
[25]
Kumar, H.; Rani, R. Structural and Optical Characterization of ZnO Nanoparticles Synthesized by Microemulsion Route, International Letters of Chemistry Physics and Astronomy, 2013, 19,. 26-36.www.scipress.com/ILCPA.19.26
[http://dx.doi.org/10.18052/www.scipress.com/ILCPA.19.26]
[26]
Maeda, H.; Khatami, M. Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs. Clin. Transl. Med., 2018, 7(1), 11.
[http://dx.doi.org/10.1186/s40169-018-0185-6] [PMID: 29541939]
[27]
Akhtar, M.J.; Ahamed, M.; Kumar, S.; Khan, M.M.; Ahmad, J.; Alrokayan, S.A. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int. J. Nanomedicine, 2012, 7, 845-857.
[http://dx.doi.org/10.2147/IJN.S29129] [PMID: 22393286]
[28]
Boyd, V.; Cholewa, O.M.; Papas, K.K. Limitations in the use of fluorescein diacetate/propidium iodide (FDA/PI) and Cell Permeable nucleic acid stains for viability measurements of isolated islets of langerhans. Curr. Trends Biotechnol. Pharm., 2008, 2(2), 66-84.
[PMID: 20814586]
[29]
Kang, T.; Guan, R.; Chen, X.; Song, Y.; Jiang, H.; Zhao, J. In vitro toxicity of different-sized ZnO nanoparticles in Caco-2 cells. Nanoscale Res. Lett., 2013, 8(1), 496.
[http://dx.doi.org/10.1186/1556-276X-8-496] [PMID: 24261419]
[30]
Wei, X.; Bugni, T.S.; Harper, M.K.; Sandoval, I.T.; Manos, E.J.; Swift, J.; Van Wagoner, R.M.; Jones, D.A.; Ireland, C.M. Evaluation of pyridoacridine alkaloids in a zebrafish phenotypic assay. Mar. Drugs, 2010, 8(6), 1769-1778.
[http://dx.doi.org/10.3390/md8061769] [PMID: 20631869]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy