Abstract :

Nanomaterials are the foundations of Nanotechnology, which are measured in nanoscales, Carbon nanotubes are one of the interesting nanomaterials, studied for over 25 years because of their superlative properties such as high surface area, electrical and thermal conductivity, high biocompatibility, flexibility, resistance to corrosion and nanosize. According to research, carbon nanotubes are applied in sensing, water treatment, and drug delivery, mainly used to deliver the anticancer drugs. In our work, functionalization of multi walled carbon nanotubes done by covalent and non-covalent functionation methods, covalent functionalization showed better dispersing efficiency in aqueous medium and compatible with biological systems with damaging the crystal lattice of carbon nanotubes. Non covalent functionalization helps to derivatized with active compounds, surface adsorption or attachment of various molecules or antibodies, which subsequently helps in targeting the site and to produce therapeutic effects. Different formulations prepared by functionalized MWCNTs and multiple functionalization of MWCNTs done by binding the drug and antibodies to prepare functionalized MWCNTs 5-Fluorouracil complexes. The Cytotoxicity assay was carried out for the obtained new targeting formulations to analyze the effect of all the formulations on HCT116 cell line. The percentage death was determined based on the viability of the cells in the appropriate vehicle controls. In this study, we report the successful functionalization, binding of 5 Fluorouracil, antibodies to MWCNTs, and cells viability of all prepared formulations for the development of novel carbon based anticancer drug delivery system. Functionalized MWCNTs-5-Fluorouracil antibodies composite at concentration above 2.5 µg/mL exhibited ≥ 50% cytotoxicity post normalization with compound control to negate precipitation observed with the compound. All the formulations showed the precipitations indicating antitumor activity and biocompatibility.

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Keywords :

Bevacizumab antibodies, Colorectal cancer, Cytotoxicity, HCT116 Cells, Multiwalled carbon nanotubes

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References :

1. Elhissi, AMA. Ahmed, W. Hassan, IU. Dhanak, VR. D’Emanuele, A. Carbon nanotubes in cancer therapy and drug delivery, J Drug Deliv 2012, pp. 1-10
2. Singla, N. and Singla, H. Novel role of nanotechnology in medicine, IJBR, 5(8), 2014, pp. 482- 486.
3. Yan, H. Xue, Z. Xie, J. Dong, Y. Toxicity of Carbon Nanotubes as Anti-Tumor Drug Carriers, Int J Nanomedicine, 14, 2019, pp. 10179–10194.
4. Saliev, T. The Advances in Biomedical Applications of Carbon Nanotubes. C, 5(29), 2019, pp. 1-22.
5. Miyashiro, D. Hamano, R. Umemura, K. A Review of Applications Using Mixed Materials of Cellulose, Nanocellulose and Carbon Nanotubes, J. Nanomater, 10(186), 2020, pp. 2-23.
6. Anzar, N. Hasan, R. Tyagi, M. Yadav, N. Narang, J. Carbon nanotube – A review on Synthesis, Properties and plethora of applications in the field of biomedical Science, Sensors International, 1, 2020, pp 1-10.
7. Hu, S. Wang, T. Pei, X. Cai, H. Chen, J. Zhang, X. Synergistic Enhancement of Antitumor Efficacy by PEGylated Multi-walled Carbon Nanotubes Modified with Cell-Penetrating Peptide TAT, Nanoscale Res Lett, 2016, pp. 1-14.
8. Wulan, P.P.D.K, Ulwani, S.H. Wulandari, H. Purwanto,W.W. Mulia, K. The effect of hydrochloric acid addition to increase carbon nanotubes dispersibility as drug delivery system by covalent functionalization, Mater. Sci. Eng. C, 2018, pp. 1-8.
9. Youssry, M. Al-Ruwaidhi, M. Zakeri, M. Zakeri, M. Physical functionalization of multiwalled carbon nanotubes for enhanced dispersibility in aqueous medium, emergent mater, 3 2020, pp, 25–32.
10. Pennetta, C. Floresta, G. Graziano, A.C.E. Cardile, V. Rubino, L. Galimberti, M. Functionalization of Single and Multi-Walled Carbon Nanotubes with Polypropylene Glycol Decorated Pyrrole for the Development of Doxorubicin Nano-Conveyors for Cancer Drug Delivery, Nanomaterials, 10( 1073), 2020, pp. 1-22.
11. Das, R. Hamid, S.B.A. Ali, M.E. Annuar, M.S.M. Samsudin, E.M.B. Bagheri, S. Covalent Functionalization Schemes for Tailoring Solubility of Multi-Walled Carbon Nanotubes in Water and Acetone Solvents, Science of Advanced Materials, 8, 2016, pp. 1-12.
12. Garnica-Gutiérrez, R.L. Lara-Martínez, L.A. Palacios, E. Masso, F. Contreras, A. Hernández-Gutiérrez, S. Effect of Functionalized Carbon Nanotubes and their Citric Acid Polymerization on Mesenchymal Stem Cells In Vitro, Journal of Nanomaterials, 2018, pp. 1-12.
13. Le, V.T. Ngo, C.L. Le, Q.T. Ngo, T. Nguyen, D.N. Vu, M.T. Surface modification and functionalization of carbon nanotube with some organic compounds, Adv. Nat. Sci: Nanosci. Nanotechnol, 4, 2013, pp. 1-5.
14. Cendrowski, K. Jedrzejczak-Silicka, M. Carbon nanotubes with controlled length – preparation, characterization and their cytocompatibility effects, Pol. J. Chem. Tech, 20(2), 2018 , pp. 71-79.
15. Ghoshal, S. Kushwaha, S.K.S. Srivastava, M. Tiwari, P. Drug Loading and Release from Functionalized Multiwalled Carbon Nanotubes Loaded With 6-Mercaptopurine Using Incipient Wetness Impregnation Method, American Journal of Advanced Drug Delivery, 2(2), 2014, pp. 213-223.
16. Ghoshal, S. Kushwaha, S.K.S. Tiwari, P. Srivastava, M. Comparative Loading and Release of 6-Mercaptopurine from Functionalized Multiwalled Carbon Nanotubes Using Various Methods, International journal of pharmacy and pharmaceutical research, 4(1), 2015, pp. 25-38.
17. Wang, C. and Li, W. Preparation, Characterization, and In Vitro and Vivo Antitumor Activity of Oridonin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group, J. Nanomater, 2016, pp. 1-7.
18. Wang, J.T.W, Spinato, C. Klippstein, R. Pach, E. Neutron-irradiated Antibodies functionalised carbon nanocapsules for targeted cancer radiotherapy, Carbon, 2020, pp. 1-31.
19. Buck, E. Sprick, M. Gaida, M.M. Grullich, C. Weber, T.F. Herpel, E. Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer, Oncol. Lett, 17, 2019, pp. 3890-3898.
20. Lia, J. Yapb, S.Q. Yoongc, S.L. Nayaka, T.R. Chandraa, G.W. Angb, W.H. Carbon nanotube bottles for incorporation, release and enhanced cytotoxic effect of cisplatin, Carbon NY, 50(4), 2019, pp. 1625-1634.
21. Wang, J.T.W. Spinato, C. Klippstein, R. Pach, E. Neutron-irradiated Antibodiesfunctionalised carbon nanocapsules for targeted cancer radiotherapy, Carbon, 2020, pp. 1-31.
22. Buck, E. Sprick, M. Gaida, M.M. Grullich, C. Weber, T.F. Herpel, E. Tumor response to irinotecan is associated with CYP3A5 expression in colorectal cancer, Oncol. Lett, 17, 2019, pp. 3890-3898.
23. Mc Devitt, M.R. Chattopadhyay, D. Kappel, B.J. Jaggi, J.S. Schiffman, S.R. Antczak, C. Tumor targetting with antibody-functionalized, radiolabeled carbon nanotubes, J Nuclear Med, 2007; 48(7), pp. 1180-1189.