Design, Synthesis, and Biological Evaluation of Camptothecin Loaded Biotinylated Cellulose Nanowhiskers as Anticancer Agents
DOI:
https://doi.org/10.22317/jcms.v7i3.960Keywords:
Keywords: Anticancer, camptothecin, cellulose nanowhiskers, biotin, glutathione.Abstract
Objective: Using biotinylated cellulose nanowhiskers (CNWs), we designed and synthesized a Glutathione (GSH) sensitive- Camptothecin (CPT) prodrug for selective CPT delivery (compound 12).
Methods: CPT-biotin (compound 9), was synthesized by direct conjugation of CPT to the biotin via GSH sensitive linkage to evaluate the role of CNWs in compound 12. The chemical structures of the synthesized prodrugs were confirmed by FT-IR, 1H NMR, 13C NMR, and ESI-MS, while the nanoparticles were characterized by DLS and TEM.
Results: The in-vitro drug release assay demonstrated that only 18.6% of CPT was released from the nano conjugate under GSH stimulation at micromolar level (100 μM), while 83.1% accumulative release rate was achieved under GSH stimulation at millimolar level (10 mM). The in-vitro cytotoxicity assay (MTT assay) demonstrated that compound 9showed higher inhibition ratios on biotin positive cells, MCF-7, and HepG2, and lower cytotoxicity on biotin negative, CHO. Compound 12 showed good activity against MCF-7, HepG2, and much lower cytotoxicity on CHO.
Conclusion: This work demonstrates CPT-biotinylated cellulose nanowhiskers for selective chemotherapy and may have the potential to be used for cancer targeting.
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2. Eggen, M.; Georg, G.I. The cryptophycins: Their synthesis and anticancer activity. Med. Res. Rev. 2002, 22, 85–101, doi:10.1002/med.10002.
3. Al-Amily, D.H.; Hassan Mohammed, M. Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group. Sci. Pharm. 2019, 87, 28, doi:10.3390/scipharm87040028.
4. Al-Darraji, A.S.; Mohamed, M.H. Synthesis and preliminary anticancer evaluation of 6-mercaptopurine-methotrexate conjugate as possible mutual prodrug. Iraqi J. Pharm. Sci. 2019, 28, 114–124, doi:10.31351/vol28iss1pp114-124.
5. Mohammed, M.H.; Taher, M.A. Synthesis of New Two Derivatives of 6-Mercaptopurine (6MP) 6-[5-Pyridine-4-yl- 1, 2, 3, 4-oxazolezole-2-yl)dithiol]-9H-purine (38) And 9H-purine-6-yl-benyldithiocarbamate (45) With Cytotoxicity Results From The National Cancer Institute’s Anticancer Drug. Int J Pharm Sci Res 2012, 3, 2613–2622.
6. Sriram, D.; Yogeeswari, P.; Thirumurugan, R.; Ratan Bal, T. Camptothecin and its analogues: A review on their chemotherapeutic potential. Nat. Prod. Res. 2005, 19, 393–412, doi:10.1080/14786410412331299005.
7. Gupta, E.; Vyas, V.; Ahmed, F.; Sinko, P.; Cook, T.; Rubin, E. Pharmacokinetics of orally administered camptothecins. Ann. N. Y. Acad. Sci. 2000, 922, 195–204, doi:10.1111/j.1749-6632.2000.tb07038.x.
8. Liu, C.; Yuan, J.; Luo, X.; Chen, M.; Chen, Z.; Zhao, Y.; Li, X. Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery. Mol. Pharm. 2014, 11, 4258–4269, doi:10.1021/mp500468d.
9. Mi, Z.; Burke, T.G. Differential Interactions of Camptothecin Lactone and Carboxylate Forms with Human Blood Components. Biochemistry 1994, 33, 10325–10336, doi:10.1021/bi00200a013.
10. Wang, J.; Cooper, R.C.; He, H.; Li, B.; Yang, H. Polyamidoamine Dendrimer Microgels: Hierarchical Arrangement of Dendrimers into Micrometer Domains with Expanded Structural Features for Programmable Drug Delivery and Release. Macromolecules 2018, 51, 6111–6118, doi:10.1021/acs.macromol.8b01006.
11. Paranjpe, P. V.; Chen, Y.; Kholodovych, V.; Welsh, W.; Stein, S.; Sinko, P.J. Tumor-targeted bioconjugate based delivery of camptothecin: Design, synthesis and in vitro evaluation. J. Control. Release 2004, 100, 275–292, doi:10.1016/j.jconrel.2004.08.030.
12. Ioelovich, M. Cellulose as a nanostructured polymer: A short review. BioResources 2008, 3, 1403–1418, doi:10.15376/biores.3.4.1403-1418.
13. Isogai, A. Wood nanocelluloses: Fundamentals and applications as new bio-based nanomaterials. J. Wood Sci. 2013, 59, 449–459, doi:10.1007/s10086-013-1365-z.
14. Abitbol, T.; Rivkin, A.; Cao, Y.; Nevo, Y.; Abraham, E.; Ben-Shalom, T.; Lapidot, S.; Shoseyov, O. Nanocellulose, a tiny fiber with huge applications. Curr. Opin. Biotechnol. 2016, 39, 76–88.
15. Xu, X.; Liu, F.; Jiang, L.; Zhu, J.Y.; Haagenson, D.; Wiesenborn, D.P. Cellulose nanocrystals vs. Cellulose nanofibrils: A comparative study on their microstructures and effects as polymer reinforcing agents. ACS Appl. Mater. Interfaces 2013, 5, 2999–3009, doi:10.1021/am302624t.
16. Klemm, D.; Schumann, D.; Udhardt, U.; Marsch, S. Bacterial synthesized cellulose - Artificial blood vessels for microsurgery. Prog. Polym. Sci. 2001, 26, 1561–1603.
17. Lemarchand, C.; Gref, R.; Couvreur, P. Polysaccharide-decorated nanoparticles. Eur. J. Pharm. Biopharm. 2004, 58, 327–341, doi:10.1016/j.ejpb.2004.02.016.
18. Eyley, S.; Thielemans, W. Surface modification of cellulose nanocrystals. Nanoscale 2014, 6, 7764–7779, doi:10.1039/c4nr01756k.
19. Fraschini, C.; Chauve, G.; Bouchard, J. TEMPO-mediated surface oxidation of cellulose nanocrystals (CNCs). Cellulose 2017, 24, 2775–2790, doi:10.1007/s10570-017-1319-5.
20. Zör, K.İ.; Amberl, O. Deactivation of Amberlite Ir-120 Used in the Esterification of Acetic Acid With Isobutanol. 2006.
21. Murar, C.E.; Thuaud, F.; Bode, J.W. KAHA ligations that form aspartyl aldehyde residues as synthetic handles for protein modification and purification. J. Am. Chem. Soc. 2014, 136, 18140–18148, doi:10.1021/ja511231f.
22. Gong, X.Y.; Yin, Y.H.; Huang, Z.J.; Lu, B.; Xu, P.H.; Zheng, H.; Xiong, F.L.; Xu, H.X.; Xiong, X.; Gu, X.B. Preparation, characterization and in vitro release study of a glutathione-dependent polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan. Int. J. Pharm. 2012, 436, 240–247, doi:10.1016/j.ijpharm.2012.06.043.
23. Zhang, X.; Breslav, M.; Grimm, J.; Guan, K.; Huang, A.; Liu, F.; Maryanoff, C.A.; Palmer, D.; Patel, M.; Qian, Y.; et al. A new procedure for preparation of carboxylic acid hydrazides. J. Org. Chem. 2002, 67, 9471–9474, doi:10.1021/jo026288n.
24. Meng, X.; Gao, M.; Deng, J.; Lu, D.; Fan, A.; Ding, D.; Kong, D.; Wang, Z.; Zhao, Y. Self-immolative micellar drug delivery: The linker matters. Nano Res. 2018, 11, 6177–6189, doi:10.1007/s12274-018-2134-5.
25. Ren, W.X.; Han, J.; Uhm, S.; Jang, Y.J.; Kang, C.; Kim, J.H.; Kim, J.S. Recent development of biotin conjugation in biological imaging, sensing, and target delivery. Chem. Commun. 2015, 51, 10403–10418, doi:10.1039/c5cc03075g.
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Published
2021-06-26
How to Cite
Wennas, O. N., Mohammed, M. H., Al Abood, R. M., & Abed, D. A. (2021). Design, Synthesis, and Biological Evaluation of Camptothecin Loaded Biotinylated Cellulose Nanowhiskers as Anticancer Agents. Journal of Contemporary Medical Sciences, 7(3), 145–151. https://doi.org/10.22317/jcms.v7i3.960
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