Log in

The Anticancer, Anti-metastatic, Anti-oxidant, and Anti-angiogenic Activity of Chitosan-coated Parthenolide/Bovine Serum Albumin Nanoparticles

  • Research
  • Published:
Journal of Inorganic and Organometallic Polymers and Materials Aims and scope Submit manuscript

Abstract

The parthenolide (PLT), a feverfew plant anticancer bioactive compound was coupled with bovine serum albumin (BSA) and coated with chitosan polymers as an appropriate biocompatible drug delivery system to evaluate its anticancer potentials on human HT-29 cancer cell line. The PLT/BSA-chitosan nanoparticles (PBC-NP) were synthesized utilizing a long-term stirring-based assembling technique. The PBC-NPs were characterized by DLS, FTIR, zeta potential, and FESEM analysis. Moreover, the PBC-NP’s cytotoxicity, anti-angiogenic, and anti-metastatic impacts were studied on the HT-29 cell line. Also, Chick chorioallantoic membrane (CAM) and scratch assays were applied to verify the anti-angiogenic and anti-metastatic potential of PBC-NP. Finally, the anti-oxidant activity of PBC-NP was measured by performing ABTS and DPPH assays. The PBC-NP (94.1 nm) decreased the HT-29 cells’survival and down-regulated VEGF/VEGF-R and MMP-9/MMP-2 gene expression, which significantly indicated their anti-angiogenic and anti-metastatic activity, respectively. Moreover, their anti-angiogenic activity was verified by detecting a significant decrease in the count and length of CAM blood vessels. Also, the decreased migration rate of HT-29 cells over the scratched line approves the PBC-NP’s anti-metastatic activity. Finally, the decreased absorbance of free ABTS and DPPH radicals following the increased PBC-NP treatment doses indicated its radical scavenging potential. The PBC-NP was successfully produced as a safe natural antioxidant and biocompatible parthenolide drug delivery system, which notably induced cellular death and decreased angiogenesis and metastasis in human colon cancer cells. Moreover, the BSA- parthenolide interaction can improve the PBC-NP efficiency by providing an intra-particle second delivery system, which will be activated upon degrading the chitosan coating shield of nanoparticles. Therefore, the PBC-NP has the potential to open a novel promising horizon in efficiently treating human colon cancer.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available upon reasonable request from the authors.

References

  1. S. Chakraborti, B.K. Ray, S. Roychoudhury, Handbook of Oxidative Stress in Cancer: Mechanistic Aspects (Springer, 2020)

  2. C. Navarro, Á Ortega, R. Santeliz, B. Garrido, M. Chacín, N. Galban et al., Metabolic reprogramming in Cancer cells: emerging Molecular Mechanisms and Novel Therapeutic Approaches. Pharmaceutics 14(6), 1303 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. P.L. de Sá Junior, D.A.D. Câmara, A.S. Porcacchia, P.M.M. Fonseca, S.D. Jorge, R.P. Araldi et al., The Roles of ROS in Cancer Heterogeneity and Therapy. Oxidative Med. Cell. Longev 2017, 2467940 (2017)

    Article  Google Scholar 

  4. D. Dakowicz, M. Zajkowska, B. Mroczko, Relationship between VEGF family members, their receptors and cell death in the Neoplastic Transformation of Colorectal Cancer. Int. J. Mol. Sci 23(6), 3375 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. H. Li, Z. Qiu, F. Li, C. Wang, The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncol. Lett. 14(5), 5865–5870 (2017)

    PubMed  PubMed Central  Google Scholar 

  6. S. Quintero-Fabián, R. Arreola, E. Becerril-Villanueva, J.C. Torres-Romero, V. Arana-Argáez, J. Lara-Riegos et al., Role of matrix metalloproteinases in angiogenesis and cancer. Front. Oncol 9, 1370 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  7. J.M. Macharia, R.W. Mwangi, N. Rozmann, K. Zsolt, T. Varjas, P.O. Uchechukwu et al., Medicinal plants with anti-colorectal cancer bioactive compounds: potential game-changers in colorectal cancer management. Biomed. Pharmacother 153, 113383 (2022)

    Article  CAS  PubMed  Google Scholar 

  8. S.D. Steichen, M. Caldorera-Moore, N.A. Peppas, A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur. J. Pharm. Sci 48(3), 416–427 (2013)

    Article  CAS  PubMed  Google Scholar 

  9. R.R. Sawant, A.M. Jhaveri, A. Koshkaryev, L. Zhu, F. Qureshi, V.P. Torchilin, Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma. Mol. Pharm 11(2), 375–381 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. S.M.R. Seyedi, A. Asoodeh, M. Darroudi, The human immune cell simulated anti-breast cancer nanorobot: the efficient, traceable, and dirigible anticancer bio-bot. Cancer Nanotechnol 13(1), 1–24 (2022)

    Article  Google Scholar 

  11. F.A. Oskooei, J. Mehrzad, A. Asoodeh, A. Motavalizadehkakhky, Multi-spectroscopic characteristics of olive oil-based Quercetin nanoemulsion (QuNE) interactions with calf thymus DNA and its anticancer activity. J. Mol. Liq 367, 120317 (2022)

    Article  Google Scholar 

  12. F. Ahmadi Oskooei, J. Mehrzad, A. Asoodeh, A. Motavalizadehkakhky, Olive oil-based quercetin nanoemulsion (QuNE)’s interactions with human serum proteins (HSA and HTF) and its anticancer activity. Journal of Biomolecular Structure and Dynamics. 2021:1–14

  13. A.P. Retnakumari, C.D. Nandan, J. Somaraj, J. Antony, V.V. Alex, B.S. Vinod et al., Chitosan Encapsulation enhances the bioavailability and tissue Retention of Curcumin and improves its efficacy in preventing B [a] P-induced lung carcinogenesis

  14. F. Pourianezhad, S. Tahmasebi, S. Nikfar, M. Mirhoseini, V. Abdusi, Review on feverfew, a valuable medicinal plant. Journal of HerbMed Pharmacology. 2016;5

  15. L.D.C. Mannelli, B. Tenci, M. Zanardelli, A. Maidecchi, A. Lugli, L. Mattoli et al., Widespread pain reliever profile of a flower extract of Tanacetum parthenium. Phytomedicine 22(7–8), 752–758 (2015)

    Article  Google Scholar 

  16. M. Sztiller-Sikorska, M. Czyz, Parthenolide as cooperating agent for anti-cancer treatment of various malignancies. Pharmaceuticals 13(8), 194 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. N.R. Penthala, V. Janganati, T.L. Alpe, S.M. Apana, M.S. Berridge, P.A. Crooks et al., N-[11CH3] Dimethylaminoparthenolide (DMAPT) uptake into orthotopic 9LSF glioblastoma tumors in the rat. Bioorg. Med. Chem. Lett 26(24), 5883–5886 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. A.M. Al-Rahim, R. AlChalabi, A.Z. Al-Saffar, G.M. Sulaiman, S. Albukhaty, T. Belali et al., Folate-methotrexate loaded bovine serum albumin nanoparticles preparation: an in vitro drug targeting cytokines overwhelming expressed immune cells from rheumatoid arthritis patients. Animal Biotechnology. 2021:1–17

  19. S. Al-Musawi, S. Albukhaty, H. Al-Karagoly, G.M. Sulaiman, M.S. Alwahibi, Y.H. Dewir et al., Antibacterial activity of honey/chitosan nanofibers loaded with capsaicin and gold nanoparticles for wound dressing. Molecules 25(20), 4770 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. C. Weber, C. Coester, J. Kreuter, K. Langer, Desolvation process and surface characterisation of protein nanoparticles. Int. J. Pharm 194(1), 91–102 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. H.H. Nguyen, J. Ryu, J.-H. Che, T.S. Kang, J.K. Lee, C.W. Song et al., Robust size control of bovine serum albumin (BSA) nanoparticles by intermittent addition of a desolvating agent and the particle formation mechanism. Food Chem 141(2), 695–701 (2013)

    Article  PubMed  Google Scholar 

  22. G.-A. Junter, P. Thébault, L. Lebrun, Polysaccharide-based antibiofilm surfaces. Acta Biomater 30, 13–25 (2016)

    Article  CAS  PubMed  Google Scholar 

  23. M. Mashreghi, M. Faal Maleki, M. Karimi, F. Kalalinia, A. Badiee, M.R. Jaafari, Improving anti-tumour efficacy of PEGylated liposomal doxorubicin by dual targeting of tumour cells and tumour endothelial cells using anti-p32 CGKRK peptide. J. Drug Target 29(6), 617–630 (2021)

    Article  CAS  PubMed  Google Scholar 

  24. N. Jafari, S. Nazeri, Z. Rabiei, S. Tahmasebi Enferadi, R. Behroozi, Growth inhibitory effect of Anthemis haussknechtii root extract, as a source of Parthenolide, on breast cancer cell line. J. Med. plants By-product 5(2), 205–210 (2016)

    Google Scholar 

  25. J. Stetefeld, S.A. McKenna, T.R. Patel, Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys. Rev 8(4), 409–427 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. B. Salopek, D. Krasic, S. Filipovic, Measurement and application of zeta-potential. Rudarsko-geolosko-naftni zbornik 4(1), 147 (1992)

    Google Scholar 

  27. P. Ramasamy, N. Subhapradha, V. Shanmugam, A. Shanmugam, Extraction, characterization and antioxidant property of chitosan from cuttlebone Sepia kobiensis (Hoyle 1885). Int. J. Biol. Macromol 64, 202–212 (2014)

    Article  CAS  PubMed  Google Scholar 

  28. A.M. Abdelgawad, M.E. El-Naggar, S.M. Hudson, O.J. Rojas, Fabrication and characterization of bactericidal thiol-chitosan and chitosan iodoacetamide nanofibres. Int. J. Biol. Macromol 94, 96–105 (2017)

    Article  CAS  PubMed  Google Scholar 

  29. K. Abrosimova, O. Shulenina, S. Paston, editors. FTIR study of secondary structure of bovine serum albumin and ovalbumin. Journal of physics: conference series; 2016: IOP Publishing

  30. M. Abbas, T. Hussain, M. Arshad, A.R. Ansari, A. Irshad, J. Nisar et al., Wound healing potential of curcumin cross-linked chitosan/polyvinyl alcohol. Int. J. Biol. Macromol 140, 871–876 (2019)

    Article  CAS  PubMed  Google Scholar 

  31. C. Qin, H. Li, Q. **ao, Y. Liu, J. Zhu, Y. Du, Water-solubility of chitosan and its antimicrobial activity. Carbohydr. Polym 63(3), 367–374 (2006)

    Article  CAS  Google Scholar 

  32. M.J. Ansari, D. Bokov, A. Markov, A.T. Jalil, M.N. Shalaby, W. Suksatan et al., Cancer combination therapies by angiogenesis inhibitors; a comprehensive review. Cell. Communication and Signaling 20(1), 1–23 (2022)

    Article  Google Scholar 

  33. Y. Fontebasso, S.M. Dubinett, Drug development for metastasis prevention. Crit. Reviews™ Oncog. 20, 5–6 (2015)

    Google Scholar 

  34. D. Weinstat-Saslow, P.S. Steeg, Angiogenesis and colonization in the tumor metastatic process: basic and applied advances. FASEB J 8(6), 401–407 (1994)

    Article  CAS  PubMed  Google Scholar 

  35. M.T. Islam, A.B. Khalipha, R. Bagchi, M. Mondal, S.Z. Smrity, S.J. Uddin et al., Anticancer activity of Thymol: a literature-based review and docking study with emphasis on its anticancer mechanisms. IUBMB life 71(1), 9–19 (2019)

    Article  CAS  PubMed  Google Scholar 

  36. Y. Zhang, M. Hu, L. Liu, X.-L. Cheng, J. Cai, J. Zhou et al., Anticancer effects of rosmarinic acid in OVCAR-3 ovarian cancer cells are mediated via induction of apoptosis, suppression of cell migration and modulation of lncRNA MALAT-1 expression. J. BUON 23(3), 763–768 (2018)

    PubMed  Google Scholar 

  37. M.A. Tomeh, R. Hadianamrei, X. Zhao, A review of curcumin and its derivatives as anticancer agents. Int. J. Mol. Sci 20(5), 1033 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. A. Rauf, M. Imran, I.A. Khan, M. ur-Rehman, S.A. Gilani, Z. Mehmood et al., Anticancer potential of quercetin: a comprehensive review. Phytother. Res 32(11), 2109–2130 (2018)

    Article  CAS  PubMed  Google Scholar 

  39. H.E. Mahood, M.K. Abbas, N.A. Zahid, Micropropagation of Feverfew (Tanacetum parthenium) and quantification of Parthenolide Content in its Micropropagated and conventionally grown plants. Horticulturae 8(1), 50 (2022)

    Article  Google Scholar 

  40. T. Gunasekaran, T. Haile, T. Nigusse, M.D. Dhanaraju, Nanotechnology: an effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac. J. Trop. Biomed. 4, S1–S7 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  41. X. Zhou, J. Lu, J. Jiang, X. Li, M. Lu, G. Yuan et al., Simple fabrication of N-doped mesoporous TiO2 nanorods with the enhanced visible light photocatalytic activity. Nanoscale Res. Lett 9(1), 1–7 (2014)

    Article  Google Scholar 

  42. J. Agnes, M.S. Muthu, P. Ajith, M. Selvakumar, M. Presheth, D.P. Anand, Preparation and characterization of Chitosan-Encapsulated Cobalt Oxide Nanoparticles modified with folic acid. Journal of Inorganic and Organometallic Polymers and Materials. 2022:1–7

  43. T.H. Abdtawfeeq, Z.A. Farhan, K. Al-Majdi, M.A. Jawad, R.S. Zabibah, Y. Riadi et al., Ultrasound-assisted and One-Pot synthesis of New Fe3O4/Mo-MOF magnetic Nano Polymer as a strong Antimicrobial Agent and efficient nanocatalyst in the Multicomponent synthesis of Novel pyrano [2, 3-d] pyrimidines derivatives. Journal of Inorganic and Organometallic Polymers and Materials. 2022:1–12

  44. M. Aida, N. Alonizan, M. Hussein, M. Hjiri, O. Abdelaziz, R. Attaf et al., Facile synthesis and antibacterial activity of bioplastic membrane containing in doped ZnO/cellulose acetate nanocomposite. J. Inorg. Organomet. Polym Mater 32(4), 1223–1233 (2022)

    Article  CAS  Google Scholar 

  45. P. Gao, G. **a, Z. Bao, C. Feng, X. Cheng, M. Kong et al., Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery. Int. J. Biol. Macromol 91, 716–723 (2016)

    Article  CAS  PubMed  Google Scholar 

  46. Y. Zhang, R. Dong, Y. Park, M. Bohner, X. Zhang, K. Ting et al., Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles. Int. J. Pharm 511(1), 79–89 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. X. Wan, X. Zheng, X. Pang, Z. Zhang, T. **g, W. Xu et al., The potential use of lapatinib-loaded human serum albumin nanoparticles in the treatment of triple-negative breast cancer. Int. J. Pharm 484(1–2), 16–28 (2015)

    Article  CAS  PubMed  Google Scholar 

  48. P.M. Carron, A. Crowley, D. O’Shea, M. McCann, O. Howe, M. Hunt et al., Targeting the folate receptor: improving efficacy in inorganic medicinal chemistry. Curr. Med. Chem 25(23), 2675–2708 (2018)

    Article  CAS  PubMed  Google Scholar 

  49. A. Karmakar, Y. Xu, T. Mustafa, G. Kannarpady, S. Bratton, A. Radominska-Pandya et al., Nanodelivery of parthenolide using functionalized nanographene enhances its anticancer activity. RSC Adv 5(4), 2411–2420 (2015)

    Article  CAS  PubMed  Google Scholar 

  50. L. Noorani, M. Stenzel, R. Liang, M.H. Pourgholami, D.L. Morris, Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model. J. Nanobiotechnol. 13(1), 1–12 (2015)

    Article  CAS  Google Scholar 

  51. M.P. Baranello, L. Bauer, C.T. Jordan, D.S. Benoit, Micelle delivery of parthenolide to acute myeloid leukemia cells. Cell. Mol. Bioeng 8(3), 455–470 (2015)

    Article  CAS  PubMed  Google Scholar 

  52. X. **, J. Zhou, Z. Zhang, H. Lv, The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis. Artif. cells Nanomed. Biotechnol. 46(sup3), S931–S942 (2018)

    Article  PubMed  Google Scholar 

  53. X. **, Q. Yang, N. Cai, Z. Zhang, A cocktail of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 in liposome systems for lung cancer treatment. Nanomedicine 15(1), 41–54 (2020)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by, Islamic Azad University, Tehran, Iran, and thus is appreciated by the author.

Funding

This research was performed at a personal expense in the laboratory of the Islamic Azad University of Tehran.

Author information

Authors and Affiliations

Authors

Contributions

Ahmed Ibrahim Albosultan: Methodology, Investigation, Formal analysis, Software, and Writing-Original draft. Maryam Ghobeh and Masoud Homayouni Tabrizi: Supervision, Data curation, Conceptualization, Validation, and Writing- Reviewing and Editing.

Corresponding author

Correspondence to Masoud Homayouni Tabrizi.

Ethics declarations

Declaration of Competing Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Albosultan, A.I., Ghobeh, M. & Tabrizi, M.H. The Anticancer, Anti-metastatic, Anti-oxidant, and Anti-angiogenic Activity of Chitosan-coated Parthenolide/Bovine Serum Albumin Nanoparticles. J Inorg Organomet Polym 33, 841–852 (2023). https://doi.org/10.1007/s10904-023-02541-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10904-023-02541-y

Keywords

Navigation