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Selective Viramidine-Loaded Aptamer-Nanoparticles Trigger Cell Cycle Arrest in Nucleolin-Expressed Hepatoma Cells Through Modulation of CDC25A/p53/PI3k Pathway

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Abstract

Active delivery of anti-cancer nanoparticles (NPs) represents a possibly influential approach, especially when treating hepatocellular carcinoma (HCC). We synthesized NPs decorated with Aptamer-AS1411 (APT), which selectively binds nucleolin on the surface of hepatoma cells. APT acts as an active targeting ligand that facilitates delivery of viramidine (VRM) against HCC cells. The conjugation between APT and NPs was confirmed by FTIR, 1H NMR, and TEM, and the resulting APT + VRM NPs were uniformly having a round shape with size of 141.77 ± 11.29 nm and zeta potential at − 43.71 ± 9.2 mV. Significant enhancement of cellular association between nucleolin and APT NPs was observed in Huh-7 more than HepG2 cells, thus, an increased cytotoxic effect against the first cell type over 2 days was seen. Furthermore, it was demonstrated that APT + VRM NPs arrest cancerous cells in G1 cell cycle phase, which is associated by a depletion in CDC25A expression. The downregulation of CDC25A is associated with overexpression of p53 and downregulation of PI3k, NF-κB, and STAT-1 expression in the nano-treated HCC cells compared with control. The outputs of protein levels showed the same pattern of the genetic expression levels of all candidates. The outcomes of this approach indicated the significant therapeutic value of APT + VRM NPs.

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References

  1. R. Siegle, D. Naishadham, and A. Jemal (2012). CA Cancer J. Clin. 62 (1), 10.

    Article  Google Scholar 

  2. A. A. Abd-Rabou and H. H. Ahmed (2017). Adv. Med. Sci. 62 (2), 357.

    Article  PubMed  Google Scholar 

  3. M. G. Hart, et al. (2011). Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD007294.pub2.

    Article  PubMed  PubMed Central  Google Scholar 

  4. J. M. Pipas, et al. (2005). J. Neuro-Oncol. 71 (3), 301.

    Article  CAS  Google Scholar 

  5. F. Alexis, et al. (2008). Mol. Pharm. 5 (4), 505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. L. Li, H. He, S. Jiang, et al. (2021). Molecules (Basel, Switzerland) 26 (5), 1271.

    Article  CAS  PubMed  Google Scholar 

  7. H. Xin, et al. (2011). Biomaterials 32 (18), 4293.

    Article  CAS  PubMed  Google Scholar 

  8. H. He, et al. (2011). Biomaterials 32 (2), 478.

    Article  CAS  PubMed  Google Scholar 

  9. S. A. Moosavian and A. Sahebkar (2019). Cancer Lett. 448, 144.

    Article  CAS  PubMed  Google Scholar 

  10. A. G. Hovanessian, et al. (2010). PloS One 5 (12), e15787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. J. Guo, et al. (2011). Biomaterials 32 (31), 8010.

    Article  CAS  PubMed  Google Scholar 

  12. H. Y. Ko, et al. (2011). Biomaterials 32, 1130.

    Article  CAS  PubMed  Google Scholar 

  13. E. M. Reyes-Reyes, Y. Teng, and P. J. Bates (2010). Cancer Res. 70 (21), 8617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. D. Legrand, et al. (2004). Eur. J. Biochem. 271 (2), 303.

    Article  CAS  PubMed  Google Scholar 

  15. X. Ji, C. Hou, et al. (2020). Food Funct. 11 (1), 163.

    Article  CAS  PubMed  Google Scholar 

  16. Y. Cheng, G. Zhao, et al. (2016). PLoS One 11 (12), e0167094.

    Article  PubMed  PubMed Central  Google Scholar 

  17. J. Al-Matouq, T. R. Holmes, et al. (2019). Mol. Carcinog. 58 (9), 1691.

    Article  CAS  PubMed  Google Scholar 

  18. Y. Song, Z. Wang, et al. (2020). J. Cell Mol. Med. 24 (23), 13739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. A. C. Girvan, Y. Teng, et al. (2006). Mol. Cancer Ther. 5 (7), 1790.

    Article  CAS  PubMed  Google Scholar 

  20. M. Szelag, J. Wesoly, et al. (2016). Curr. Protein Pept. Sci. 17 (2), 135.

    Article  CAS  PubMed  Google Scholar 

  21. A. A. Abd-Rabou, D. J. Bharali, and S. A. Mousa (2020). Appl. Biochem. Biotechnol. 190 (1), 305.

    Article  CAS  PubMed  Google Scholar 

  22. A. A. Abd-Rabou, D. J. Bharali, and S. A. Mousa (2018). Pharm. Res. 35 (4), 1.

    Article  CAS  Google Scholar 

  23. B. M. Rothen-Rutishauser, et al. (2006). Environ. Sci. Technol. 40 (14), 4353.

    Article  CAS  PubMed  Google Scholar 

  24. X. Gao, et al. (2006). Biomaterials 27 (18), 3482.

    Article  CAS  PubMed  Google Scholar 

  25. J. Cheng, et al. (2007). Biomaterials 28 (5), 869.

    Article  CAS  PubMed  Google Scholar 

  26. A. Aravind, et al. (2012). Biotechnol Bioeng 109 (11), 2920.

    CAS  Google Scholar 

  27. J. Van Meerloo, G. J. Kaspers, and J. Cloos, in Cancer Cell Culture (Springer, Berlin, 2011), pp 237–245.

    Chapter  Google Scholar 

  28. M. Koutsioumpa, et al. (2013). J. Biol. Chem. 288 (1), 343.

    Article  CAS  PubMed  Google Scholar 

  29. H. Chen, et al. (2013). J. Biotechnol. 168 (4), 362.

    Article  CAS  PubMed  Google Scholar 

  30. C. F. Semenkovich, et al. (1990). Biochemistry 29 (41), 9708.

    Article  CAS  PubMed  Google Scholar 

  31. Y. Cho, et al. (2016). PloS One 11 (8), e0160822.

    Article  PubMed  PubMed Central  Google Scholar 

  32. L. Zhao, X. Qi, et al. (2019). J. Am. Chem. Soc. 141 (44), 17493.

    Article  CAS  PubMed  Google Scholar 

  33. K. Y. Lee, et al. (2010). J. Biomed. Biotechnol. 2010, 1.

    Google Scholar 

  34. C. R. Ireson and L. R. Kelland (2006). Mol Cancer Ther. 5 (12), 2957.

    Article  CAS  PubMed  Google Scholar 

  35. E. W. Ng, et al. (2006). Nat. Rev. Drug Discov. 5 (2), 123.

    Article  CAS  PubMed  Google Scholar 

  36. A. Keefe, S. Pai, and A. Ellington (2010). Nat. Rev. Drug Discov. 9, 537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. M. Ahmed and R. Narain (2015). Nanomedicine 10 (14), 2263.

    Article  CAS  PubMed  Google Scholar 

  38. J. Varshosaz, et al. (2012). J. Liposome Res. 22 (3), 224.

    Article  CAS  PubMed  Google Scholar 

  39. D.-C. Li, et al. (2009). J. Controlled Release 138 (2), 103.

    Article  CAS  Google Scholar 

  40. F. Marcucci and F. Lefoulon (2004). Drug Discov. Today 9 (5), 219.

    Article  CAS  PubMed  Google Scholar 

  41. B. Song, et al. (2009). Colloids Surf. B Biointerfaces 70 (2), 181.

    Article  CAS  PubMed  Google Scholar 

  42. Q. Gan, et al. (2005). Colloids Surf. B Biointerfaces 44 (2–3), 65.

    Article  CAS  PubMed  Google Scholar 

  43. M. Cheng, et al. (2012). PloS One 7, e47115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. K. Ninomiya, et al. (2013). Bioorg. Med. Chem. Lett. 23 (6), 1797.

    Article  CAS  PubMed  Google Scholar 

  45. D. Sun, et al. (2015). Anal. Chim. Acta 885, 166.

    Article  CAS  PubMed  Google Scholar 

  46. J. Yu, et al. (2020). Nanoscale Res. Lett. 15 (1), 1.

    Article  Google Scholar 

  47. Y. Cho, et al. (2016). Dig. Dis. Sci. 61 (9), 2568.

    Article  CAS  PubMed  Google Scholar 

  48. F. Mongelard and P. Bouvet (2010). Curr. Opin. Mol. Ther. 12 (1), 107.

    CAS  PubMed  Google Scholar 

  49. J. E. Rosenberg, et al. (2014). Investig. New Drugs 32 (1), 178.

    Article  CAS  Google Scholar 

  50. B. E. Eaton, et al. (1997). Bioorg. Med. Chem. 5 (6), 1087.

    Article  CAS  PubMed  Google Scholar 

  51. A. A. Abd-Rabou and A. E. Edris (2021). Cancer Nanotechnol. 12 (1), 28.

    Article  CAS  Google Scholar 

  52. A. A. Abd-Rabou, A. M. Abdelaziz, O. G. Shaker, and G. Ayeldeen (2021). Mol. Biol. Rep. 48 (10), 6805.

    Article  CAS  PubMed  Google Scholar 

  53. L. Chen, M. He, et al. (2021). Pharmacol. Ther. (Oxford) 226, 107868.

    Article  CAS  Google Scholar 

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Funding

The authors declare that this publication was funded from National Research Centre to Ass. Prof. AA Abd-Rabou (Grant No. 12060129).

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Authors and Affiliations

  1. Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Giza, 12622, Egypt

    Ahmed A. Abd-Rabou, Hanaa H. Ahmed & Mohamed S. Kishta

  2. Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, 12622, Egypt

    Ahmed A. Abd-Rabou, Hanaa H. Ahmed & Mohamed S. Kishta

  3. Cell Biology Department, Biotechnology Research Institute, National Research Centre, Giza, 12622, Egypt

    Khairy M. A. Zoheir

Authors
  1. Ahmed A. Abd-Rabou
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  2. Hanaa H. Ahmed
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  3. Mohamed S. Kishta
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  4. Khairy M. A. Zoheir
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Contributions

All authors contributed in this study. AAA, the corresponding author, conceived the research idea, synthesized and characterized the NPs, as well as performed cell culture, cytotoxicity, flow cytometry, biochemical and genetic experiments, data analysis, wrote the manuscript, and responsible for publication. MSK and HHA participated in cytotoxicity and biochemical experiments. HHA shared in the analysis and editing the manuscript. KMMZ participated in the genetic and protein experiments.

Corresponding author

Correspondence to Ahmed A. Abd-Rabou.

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The protocol of this article is ethically approved by the Ethical Committee for Medical Research, National Research Centre (Approval No. 19/200).

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It is an in vitro study on cell lines.

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Abd-Rabou, A.A., Ahmed, H.H., Kishta, M.S. et al. Selective Viramidine-Loaded Aptamer-Nanoparticles Trigger Cell Cycle Arrest in Nucleolin-Expressed Hepatoma Cells Through Modulation of CDC25A/p53/PI3k Pathway. J Clust Sci 34, 335–348 (2023). https://doi.org/10.1007/s10876-022-02224-7

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  • DOI: https://doi.org/10.1007/s10876-022-02224-7

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