Skip to main content

Advertisement

SpringerLink
Log in

Deciphering the anticancer activity of biocompatible zinc oxide nanoparticles loaded with methotrexate on breast cancer cells

  • Published:
Bulletin of Materials Science Aims and scope Submit manuscript

Abstract

Novel nanoparticle-based therapies, in combination with cytotoxic drugs, are a new paradigm that is being explored. Methotrexate (MTX), a folic acid (FA) analog, is internalized by the folic acid receptor (FAR) which is known to be overexpressed in many cancer cells like breast cancer. MTX suppresses cell division by binding and blocking the dihydrofolate reductase, resulting in cell death due to cell cycle arrest. Thus, targeting FAR is an attractive strategy for controlling breast cancer cells. Zinc oxide nanoparticles (ZnONPs) are known biocompatible agents with anticancer and antimicrobial properties. Both MTX and ZnONPs have limitations such as nonspecific absorption and toxicity. In this study, we have attempted to use a combinatorial approach using MTX and ZnONPs, to target FAR on breast cancer cells and to improve the specificity towards cancer cells and be safe towards normal cells. Cytotoxicity of MTX–ZnONPs was assessed via MTT assay and acridine orange/ethidium bromide staining, which showed specificity and anticancer potential towards MTX-sensitive MCF-7 and MTX-resistant MDA-MB-231 cell lines, while showing less toxicity towards MCF-10A control cells. Also, the RBC haemolysis assay supports the biocompatible nature of MTX–ZnONPs, showing no haemolysis. Our results reveal MTX–ZnONPs as a novel nanosystem for showing specificity and cytotoxicity towards breast cancer cells, including MTX-resistant MDA-MB-231.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. Gao X, Li X and Yu W 2005 J. Phys. Chem. B 109 1155

    Article  CAS  Google Scholar 

  2. Ravichandrika K and Kiranmayirvssnr P 2012 Adv. Mater. Res. 585 154

    Article  Google Scholar 

  3. Chang Y N, Zhang M, Xia L, Zhang J and Xing G 2012 Materials 5 2850

    Article  CAS  Google Scholar 

  4. Kim K M, Kim T H, Kim H M, Kim H J, Gwak G H, Paek S M et al 2012 Toxicol. Environ. Health Sci. 4 121

    Article  Google Scholar 

  5. Zhang Y, Nayak T, Hong H and Cai W 2013 Curr. Mol. Med. 13 1633

    Article  CAS  Google Scholar 

  6. Shobhaa N, Nandab N and Nagabhushana B M 2017 Mapana J. Sci. 16 41

    Article  Google Scholar 

  7. Hanley C, Layne J, Punnoose A, Reddy K, Coombs I, Coombs A et al 2008 Nanotechnology 19 1

    Article  Google Scholar 

  8. Puvvada N, Rajput S, Kumar B N, Sarkar S, Konar S, Brunt K R et al 2015 Sci. Rep. 5 1

    Article  Google Scholar 

  9. Premanathan M, Karthikeyan K, Jeyasubramanian K and Manivannan G 2011 Nanomedicine 7 184

    Article  CAS  Google Scholar 

  10. Nithya A and Jothivenkatachalam K 2015 J. Mater. Sci. Mater. Electron. 26 10207

    Article  CAS  Google Scholar 

  11. Wu H and Zhang J 2018 Saudi Pharm. J. 26 205

    Article  Google Scholar 

  12. Dragojevic S, Ryu J S and Raucher D 2015 Molecules 20 21750

    Article  CAS  Google Scholar 

  13. Chieng B W and Loo Y Y 2012 Mater. Lett. 73 78

    Article  CAS  Google Scholar 

  14. Nosrati H, Salehiabar M, Davaran S, Danafar H and Manjili H K 2017 Drug Dev. Ind. Pharm. 44 886

    Article  Google Scholar 

  15. Johari-Ahar M, Barar J, Alizadeh A M, Davaran S, Omidi Y and Rashidi M R 2016 J. Drug Target. 24 120

    Article  CAS  Google Scholar 

  16. Alavi A S and Meshkini A 2018 Eur. J. Pharm. Sci. 115 144

    Article  CAS  Google Scholar 

  17. De Oliveira C P, Büttenbender S L, Prado W A, Beckenkamp A, Asbahr A C, Buffon A et al 2018 Nanomaterials 8 24

    Article  Google Scholar 

  18. Garg N K, Singh B, Jain A, Nirbhavane P, Sharma R, Tyagi R K et al 2016 Colloids Surf. B Biointerfaces 146 114

    Article  CAS  Google Scholar 

  19. Wong P T and Choi S K 2015 Int. J. Mol. Sci. 16 1772

    Article  CAS  Google Scholar 

  20. Majoros I J, Williams C R, Becker A and Baker J R 2009 Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1 502

    Article  CAS  Google Scholar 

  21. Rahman M, Khan J A, Kanwal U, Awan U A and Raza A 2021 J. Nanopart. Res. 23 195

    Article  CAS  Google Scholar 

  22. Agabeigi R, Rasta S H, Rahmati-Yamchi M, Salehi R and Alizadeh E 2020 Nanoscale Res. Lett. 15 1

    Article  Google Scholar 

  23. Chen J, Huang L, Lai H, Lu C, Fang M, Zhang Q et al 2014 Mol. Pharm. 11 2213

    Article  CAS  Google Scholar 

  24. Jadhav V, Ray P, Sachdeva G and Bhatt P 2016 Life Sci. 148 41

    Article  CAS  Google Scholar 

  25. Shinde V and Desai K 2022 J. Biomed. Mater. Res. B Appl. Biomater. 110 1400

    Article  CAS  Google Scholar 

  26. Hoonjan M, Sachdeva G, Chandra S, Kharkar P S, Sahu N and Bhatt P 2018 Nanoscale 10 8031

    Article  CAS  Google Scholar 

  27. Raoufi D 2013 Renew. Energy 50 932

    Article  CAS  Google Scholar 

  28. Singh S, Singh B, Sharma P, Mittal A, Kumar S, Saini G S et al 2017 Mater. Des. 134 10

    Article  CAS  Google Scholar 

  29. Buchheit R, Acosta-Humanez F and Almanzaby O 2016 Rev. Cubana Fisica 33 4

    Google Scholar 

  30. Wu Q, Chen X, Zhang P, Han Y, Chen X, Yan Y et al 2008 Cryst. Growth Des. 8 3010

    Article  CAS  Google Scholar 

  31. Bhatkalkar S G, Kumar D, Ali A and Sachar S 2018 J. Mol. Liq. 268 1

    Article  CAS  Google Scholar 

  32. Sanmugam A, Vikraman D, Park H and Kim H-S 2017 Nanomaterials 7 363

    Article  Google Scholar 

  33. Akhtar M J, Ahamed M, Kumar S, Khan M M, Ahmad J and Alrokayan S A 2012 Int. J. Nanomed. 7 845

    CAS  Google Scholar 

  34. Malaikozhundan B, Vaseeharan B, Vijayakumar S, Pandiselvi K, Kalanjiam M A, Murugan K et al 2017 Microb. Pathog. 104 268

    Article  CAS  Google Scholar 

  35. Yu J, Baek M, Chung H E and Choi S J 2011 J. Phys. Conf. Ser. 304 012044

    Article  Google Scholar 

  36. Albanese A, Tang P S and Chan W C W 2012 Annu. Rev. Biomed. Eng. 14 1

    Article  CAS  Google Scholar 

  37. Sandmann A, Kompch A, Mackert V, Liebscher C H and Winterer M 2015 Langmuir 31 5701

    Article  CAS  Google Scholar 

  38. Lanje A S, Sharma S J, Ningthoujam R S, Ahn J S and Pode R B 2013 Adv. Powder Technol. 24 331

    Article  CAS  Google Scholar 

  39. AbdElhady M M 2012 Int. J. Carbohydr. Chem. 2012 6

    Article  Google Scholar 

  40. Kumari S D C, Tharani C B, Narayanan N and Kumar C S 2013 Indian J. Res. Pharm. Biotechnol. 1 915

    Google Scholar 

  41. Xie X, Liao J, Shao X, Li Q and Lin Y 2017 Sci. Rep. 7 3827

    Article  Google Scholar 

  42. Ahamed A J and Vijaya Kumar P 2016 J. Chem. Pharm. Res. 8 624

    CAS  Google Scholar 

  43. Boruah S, Mustafiza S, Saikia D, Saikia H J, Saikia P P and Baruah M K 2016 Am. Chem. Sci. J. 11 1

    Article  CAS  Google Scholar 

  44. Sreevalsa V G, Jeeju P P, Augustine M S, Anilkumar K M and Jayalekshmi S 2013 J. Exp. Nanosci. 8 937

    Article  CAS  Google Scholar 

  45. Liu J, Park J, Park K H, Ahn Y, Park J Y, Koh K H et al 2010 Nanotechnology 21 485

    Google Scholar 

  46. Liu J, Ma X, Jin S, Xue X, Zhang C, Wei T et al 2016 Mol. Pharm. 13 1723

    Article  CAS  Google Scholar 

  47. Xiong H M 2013 Adv. Mater. 25 5329

    Article  CAS  Google Scholar 

  48. Rasmussen J W, Martinez E, Louka P and Wingett D G 2010 Expert Opin. Drug Deliv. 7 1063

    Article  CAS  Google Scholar 

  49. Bryan J 2012 Pharm. J. 289 303

    Google Scholar 

  50. Hess J A and Khasawneh M K 2015 BBA Clin. 3 152

    Article  Google Scholar 

  51. Bath R K, Brar N K, Forouhar F A and Wu G Y 2014 J. Dig. Dis. 15 517

    Article  CAS  Google Scholar 

  52. Worm J, Kirkin A F, Dzhandzhugazyan K N and Guldberg P 2001 J. Biol. Chem. 276 39990

    Article  CAS  Google Scholar 

  53. Corona G, Giannini F, Fabris M, Toffoli G and Boiocchi M 1998 Int. J. Cancer 75 125

    Article  CAS  Google Scholar 

  54. Liu K, Liu P, Liu R and Wu X 2015 Med. Sci. Monit. Basic Res. 21 15

    Article  Google Scholar 

  55. Taylor I W and Tattersall M H 1981 Cancer Res. 41 1549

    CAS  Google Scholar 

  56. Grönroos M, Chen M, Jahnukainen T, Capitanio A, Aizman R I and Celsi G 2006 Pediatr. Blood Cancer 46 624

    Article  Google Scholar 

  57. El-Waseif A 2019 J. Arab. Soc. Med. Res. 14 42

    Article  Google Scholar 

  58. PreediaBabu E, Subastri A, Suyavaran A, Premkumar K, Sujatha V and Aristatile B 2017 Sci. Rep. 7 1

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the Department of MEMS, IIT Bombay, for XRD analysis and SAIF, IIT Bombay, for ICP-AES, SEM-EDS and HR-TEM facilities. We also acknowledge Khandelwal Laboratories Pvt. Ltd, Mumbai, India, for providing an MTX gift sample. We would also like to thank Dr Padma V Devarajan and Dr K C Barick for their insightful suggestions in the research work.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Sunandan Divatia School of Science, SVKM’s NMIMS (Deemed-to-be University), Mumbai, 400056, India

    Mitesh Joshi & Purvi Bhatt

Authors
  1. Mitesh Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Purvi Bhatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Purvi Bhatt.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joshi, M., Bhatt, P. Deciphering the anticancer activity of biocompatible zinc oxide nanoparticles loaded with methotrexate on breast cancer cells. Bull Mater Sci 46, 192 (2023). https://doi.org/10.1007/s12034-023-03044-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12034-023-03044-9

Keywords

Search

Navigation