Preparation of zinc oxide-carboxymethyl cellulose blended with cyclophosphamide for targeted drug delivery to lung adenocarcinoma cells

K. Harsha Prabha; Mahalakshmi Nannan; Sivaramakrishnan Venkatabalasubramanian

doi:10.7324/JABB.2023.145826

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Abstract

Lung adenocarcinoma represents more than 40% of global lung cancer cases diagnosed yearly. Nano-drug delivery systems made from polymeric nanocomposites (NCs) have been described as promising carriers of chemotherapeutic payload against lung adenocarcinoma. Zinc oxide (ZnO) nanoparticles, which have been shown to produce tumor-selective cell death, lower treatment resistance, and lower side effects in vitro, are excellent therapeutic systems that can be combined with chemotherapeutic agents. Using the chemical reduction method, we prepared ZnO nanoparticles in this study and embedded them in non-toxic adsorbent carboxymethyl cellulose (CMC). This polymeric nanocomposite (NC) was further blended with cyclophosphamide (CPS): A hydrophobic chemotherapeutic drug and analyzed for its cytotoxicity against lung adenocarcinoma cells. Characterization of NCs was performed by UV-visible spectroscopy, dynamic light scattering, Fourier-transform-infrared spectroscopy, and transmission electron microscopy. MTT analysis revealed that the biological cytotoxic potential of ZnO-CMC-CPS NCs was superior to ZnO-CMC NCs against A549 cells. Furthermore, Western blot analysis for Ki-67 (proliferation biomarker) expression analysis was performed for ZnO entrapped CMC NC versus ZnO-CMC-CPS-treated lung adenocarcinoma cells. ZnO-CMC-CPS NCs revealed a superior decrease in Ki-67 expression compared to ZnO-CMC alone treated lung adenocarcinoma cells. These results indicate that the synthesized ZnO-CMC-CPS polymeric NC, compared to ZnO-CMC, is an efficient drug delivery system with anti-proliferative potential and augmented cytotoxicity against lung adenocarcinoma cells. These polymeric NCs are prospective drug delivery systems for antiproliferative therapy.

Keyword: Polymeric nanocomposites Lung cancer Cyclophosphamide Carboxymethyl cellulose Zinc oxide

Citation:

Prabha KH, Nannan M, Venkatabalasubramanian S. Preparation of zinc oxide-carboxymethyl cellulose blended with cyclophosphamide for targeted drug delivery to lung adenocarcinoma cells. J App Biol Biotech. 2023;11(Suppl 1):40-45. http://doi.org/10.7324/JABB.2023.145826

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

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Reference

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1. Sudhakar A. History of cancer, ancient and modern treatment methods. J Cancer Sci Ther 2009;1:1-4. https://doi.org/10.4172/1948-5956.100000e2

2. Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: Biology and treatment options. Biochim Biophys Acta 2015;1856:189-210. https://doi.org/10.1016/j.bbcan.2015.08.002

3. Wei MM, Zhou GB. Long non-coding RNAs and their roles in non-small-cell lung cancer. Genomics Proteomics Bioinformatics 2016;14:280-8. https://doi.org/10.1016/j.gpb.2016.03.007

4. Sadhukhan P, Kundu M, Chatterjee S, Ghosh N, Manna P, Das J, et al. Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy. Mater Sci Eng C Mater Biol Appl 2019;100:129-40. https://doi.org/10.1016/j.msec.2019.02.096

5. Sinha R, Kim GJ, Nie S, Shin DM. Nanotechnology in cancer therapeutics: Bioconjugated nanoparticles for drug delivery. Mol Cancer Ther 2006;5:1909-17. https://doi.org/10.1158/1535-7163.MCT-06-0141

6. Wang X, Yang L, Chen ZG, Shin DM. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin 2008;58:97-110. https://doi.org/10.3322/CA.2007.0003

7. Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: Application of nanotechnology in cancer therapy. Drug Discov Today 2010;15:842-50. https://doi.org/10.1016/j.drudis.2010.08.006

8. Mohanraj VJ, Chen Y. Nanoparticles-a review. Trop J Pharm Res 2006;5:561-73. https://doi.org/10.4314/tjpr.v5i1.14634

9. Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol Rep 2012;64:1020-37. https://doi.org/10.1016/S1734-1140(12)70901-5

10. Raj S, Khurana S, Choudhari R, Kesari KK, Kamal MA, Garg N, et al. Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. Semin Cancer Biol 2021;69:166-77. https://doi.org/10.1016/j.semcancer.2019.11.002

11. Pan L, Liu J, Shi J. Cancer cell nucleus-targeting nanocomposites for advanced tumor therapeutics. Chem Soc Rev 2018;47:6930-46. https://doi.org/10.1039/C8CS00081F

12. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol 2009;86:215-23. https://doi.org/10.1016/j.yexmp.2008.12.004

13. Chamundeeswari M, Jeslin J, Verma ML. Nanocarriers for drug delivery applications. Environ Chem Lett 2019;17:849-65. https://doi.org/10.1007/s10311-018-00841-1

14. Camargo PH, Satyanarayana KG, Wypych F. Nanocomposites: Synthesis, structure, properties and new application opportunities. Mater Res 2009;12:1-39. https://doi.org/10.1590/S1516-14392009000100002

15. Hanafy NA, Leporatti S, El-Kemary M. Mucoadhesive curcumin crosslinked carboxy methyl cellulose might increase inhibitory efficiency for liver cancer treatment. Mater Sci Eng C 2020;116:111119. https://doi.org/10.1016/j.msec.2020.111119

16. Basta AH, El-Saied H, El-Deftar MM, El-Henawy AA, El-Sheikh HH, Abdel-Shakour EH, et al. Properties of modified carboxymethyl cellulose and its use as bioactive compound. Carbohydr Polym 2016;153:641-51. https://doi.org/10.1016/j.carbpol.2016.07.051

17. Rao Z, Ge H, Liu L, Zhu C, Min L, Liu M, et al. Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system. Int J Biol Macromol 2018;107:1184-92. https://doi.org/10.1016/j.ijbiomac.2017.09.096

18. Javanbakht S, Shaabani A. Carboxymethyl cellulose-based oral delivery systems. Int J Biol Macromol 2019;133:21-9. https://doi.org/10.1016/j.ijbiomac.2019.04.079

19. Upadhyaya L, Singh J, Agarwal V, Pandey AC, Verma SP, Das P, et al. In situ grafted nanostructured ZnO/carboxymethyl cellulose nanocomposites for efficient delivery of curcumin to cancer. J Polym Res 2014;21:550. https://doi.org/10.1007/s10965-014-0550-0

20. Premanathan M, Karthikeyan K, Jeyasubramanian K, Manivannan G. Selective toxicity of ZnO nanoparticles toward gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomedicine 2011;7:184-92. https://doi.org/10.1016/j.nano.2010.10.001

21. Akhtar MJ, Ahamed M, Kumar S, Khan MM, Ahmad J, Alrokayan SA. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int J Nanomedicine 2012;7:845-57. https://doi.org/10.2147/IJN.S29129

22. Queirós V, Azeiteiro UM, Soares AM, Freitas R. The antineoplastic drugs cyclophosphamide and cisplatin in the aquatic environment-review. J Hazard Mater 2021;412:125028. https://doi.org/10.1016/j.jhazmat.2020.125028

23. Iqubal A, Iqubal MK, Sharma S, Ansari MA, Najmi AK, Ali SM, et al. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci 2019;218:112-31. https://doi.org/10.1016/j.lfs.2018.12.018

24. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: Golden anniversary. Nat Rev Clin Oncol 2009;6:638-47. https://doi.org/10.1038/nrclinonc.2009.146

25. Armelao L, Bottaro G, Bovo L, MacCato C, Tondello E, Anselmi F, et al. Proteins conjugation with ZnO sol-gel nanopowders. J Solgel Sci Technol 2011;60:352-8. https://doi.org/10.1007/s10971-011-2504-x

26. Luna-Martínez JF, Hernández-Uresti DB, Reyes-Melo ME, Guerrero- Salazar CA, González-González VA, Sepúlveda-Guzmán S. Synthesis and optical characterization of ZnS-sodium carboxymethyl cellulose nanocomposite films. Carbohydr Polym 2011;84:566-70. https://doi.org/10.1016/j.carbpol.2010.12.021

27. Awan F, Islam MS, Ma Y, Yang C, Shi Z, Berry RM, et al. Cellulose nanocrystal-ZnO nanohybrids for controlling photocatalytic activity and UV protection in cosmetic formulation. ACS Omega 2018;3:12403-11. https://doi.org/10.1021/acsomega.8b01881

28. Rigano L, Lionetti N. Nanobiomaterials in galenic formulations and cosmetics. In: Nanobiomaterials in Galenic Formulations and Cosmetics: Applications of Nanobiomaterials. Amsterdam: Elsevier; 2016. p. 121-48. https://doi.org/10.1016/B978-0-323-42868-2.00006-1

29. Wolinsky JB, Grinstaff MW. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Deliv Rev 2008;60:1037-55. https://doi.org/10.1016/j.addr.2008.02.012

30. Pandey H, Rani R, Agarwal V. Liposome and their applications in cancer therapy. Braz Arch Biol Technol 2016;59:e16150477. https://doi.org/10.1590/1678-4324-2016150477

31. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: Classification, preparation, and applications. Nanoscale Res Lett 2013;8:102. https://doi.org/10.1186/1556-276X-8-102

32. López-Dávila V, Seifalian AM, Loizidou M. Organic nanocarriers for cancer drug delivery. Curr Opin Pharmacol 2012;12:414-9. https://doi.org/10.1016/j.coph.2012.02.011

33. Eatemadi A, Daraee H, Karimkhanloo H, Kouhi M, Zarghami N, Akbarzadeh A, et al. Carbon nanotubes: Properties, synthesis, purification, and medical applications. Nanoscale Res Lett 2014;9:393. https://doi.org/10.1186/1556-276X-9-393

34. Jagadeesh P, Sowmya K, Radhika PR, Kumar ST. Carbon nanotubes: The future of cancer treatment. Int J Pharma Sci Res 2011;2:217-24.

35. Dragar ?, Potr? T, Nemec S, Roškar R, Pajk S, Kocbek P, et al. One-pot method for preparation of magnetic multi-core nanocarriers for drug delivery. Materials (Basel) 2019;12:540. https://doi.org/10.3390/ma12030540

36. Rivas J, Bañobre-López M, Piñeiro-Redondo Y, Rivas B, López- Quintela MA. Magnetic nanoparticles for application in cancer therapy. J Magn Magn Mater 2012;324:3499-502. https://doi.org/10.1016/j.jmmm.2012.02.075