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Enhanced Antitumor and Antimetastatic Activity of pH-Responsive Curcumin-Loaded Chitosan-Selenium Nanocomposites against Breast Cancer

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Abstract

Due to low toxicity and anti-cancer activity, selenium nanoparticles have been studied to treat various cancers. In the present study, curcumin-loaded selenium-chitosan nanocomposites (CUR-Cs-SeNCs) were prepared, and their inhibitory effect on 4T1 cell line and tumor-bearing mice was reported. FTIR, XRD, EDX, AFM, and SEM analysis confirmed the successful preparation of CUR-Cs-SeNCs. The average size, polydispersity index, and zeta potential of CUR-Cs-SeNCs were 167.43 ± 6.52, 0.18 ± 0.05, and 35.62 ± 5.21 mV, respectively. The cumulative released percentage of curcumin from nanocomposites at pH 5.5 was about 1.8 times higher than at pH 7.4. Moreover, CUR-Cs-SeNCs showed a diffusion-controlled release pattern at pH 6.8 and 5.5. The in vitro cytotoxicity study on 4T1 cells revealed that CUR-Cs-SeNCs dramatically reduced cell proliferation rate compared to pure curcumin. Additionally, the in vivo study confirmed that the CUR-Cs-SeNCs were more successful in reducing the tumor volume than net CUR. More importantly, histopathological studies revealed a more substantial inhibitory effect on tumor growth and liver metastasis of CUR-Cs-SeNCs as compared to free curcumin. No significant signs of toxicity were detected in the vital organs of CUR-Cs-SeNCs-receiving animals. Therefore, considering the pH-dependent release, the improved inhibitory effect on turmeric cells, and the outstanding performance in the animal model, the CUR-Cs-SeNCs may be promising in future tumor management.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Miller, K. D., et al. (2021). Cancer statistics for the US Hispanic/Latino population. CA: A Cancer Journal for Clinicians, 71(6), 466–487.

    Google Scholar 

  2. Carty, N., Foggitt, A., Hamilton, C., Royle, G., & Taylor, I. (1995). Patterns of clinical metastasis in breast cancer: An analysis of 100 patients. European Journal of Surgical Oncology (EJSO), 21(6), 607–608.

    Article  Google Scholar 

  3. Kumar, A., et al. (2020). Deep feature learning for histopathological image classification of canine mammary tumors and human breast cancer. Information Sciences, 508, 405–421.

    Article  Google Scholar 

  4. El-Hussein, A., Manoto, S. L., Ombinda-Lemboumba, S., Alrowaili, Z. A., & Mthunzi-Kufa, P. (2021). A review of chemotherapy and photodynamic therapy for lung cancer treatment. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 21(2), 149–161.

    Google Scholar 

  5. Zoi, V., Galani, V., Lianos, G. D., Voulgaris, S., Kyritsis, A. P., & Alexiou, G. A. (2021). The role of curcumin in cancer treatment. Biomedicines, 9(9), 1086.

    Article  Google Scholar 

  6. Goycoolea, F. M., & Milkova, V. (2017). Electrokinetic behavoir of chitosan adsorbed on o/w nanoemulsion droplets. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 519, 205–211.

    Article  Google Scholar 

  7. Helzlsouer, K. J., et al. (2000). Association between α-tocopherol, γ-tocopherol, selenium, and subsequent prostate cancer. JNCI: Journal of the National Cancer Institute, 92(24), 2018–2023.

    Article  Google Scholar 

  8. Kong, L., et al. (2011). The suppression of prostate LNCaP cancer cells growth by Selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis. Biomaterials, 32(27), 6515–6522.

    Article  Google Scholar 

  9. Liu, T., et al. (2020). Selenium nanoparticles regulates selenoprotein to boost cytokine-induced killer cells-based cancer immunotherapy. Nano Today, 35, 100975.

    Article  Google Scholar 

  10. Micke, O., Schomburg, L., Buentzel, J., Kisters, K., & Muecke, R. (2009). Selenium in oncology: From chemistry to clinics. Molecules, 14(10), 3975–3988.

    Article  Google Scholar 

  11. Liu, T., Zeng, L., Jiang, W., Fu, Y., Zheng, W., & Chen, T. (2015). “Rational design of cancer-targeted selenium nanoparticles to antagonize multidrug resistance in cancer cells,” Nanomedicine: Nanotechnology. Biology and Medicine, 11(4), 947–958.

    Google Scholar 

  12. Varlamova, E. G., et al. (2021). Mechanisms of the cytotoxic effect of selenium nanoparticles in different human cancer cell lines. International Journal of Molecular Sciences, 22(15), 7798.

    Article  Google Scholar 

  13. Ren, Y., et al. (2013). Antitumor activity of hyaluronic acid–selenium nanoparticles in Heps tumor mice models. International Journal of Biological Macromolecules, 57, 57–62.

    Article  Google Scholar 

  14. Sonkusre, P., & Cameotra, S. S. (2017). Biogenic selenium nanoparticles induce ROS-mediated necroptosis in PC-3 cancer cells through TNF activation. Journal of Nanobiotechnology, 15(1), 1–12.

    Article  Google Scholar 

  15. Islam, W., Niidome, T., & Sawa, T. (2022). Enhanced permeability and retention effect as a ubiquitous and epoch-making phenomenon for the selective drug targeting of solid tumors. Journal of Personalized Medicine, 12(12), 1964.

    Article  Google Scholar 

  16. Wang, Y., et al. (2015). Inverse relationship between elemental selenium nanoparticle size and inhibition of cancer cell growth in vitro and in vivo. Food and Chemical Toxicology, 85, 71–77.

    Article  Google Scholar 

  17. Wang, X., Sun, K., Tan, Y., Wu, S., & Zhang, J. (2014). Efficacy and safety of selenium nanoparticles administered intraperitoneally for the prevention of growth of cancer cells in the peritoneal cavity. Free Radical Biology and Medicine, 72, 1–10.

    Article  Google Scholar 

  18. Li, Y., et al. (2020). A pH-sensitive drug delivery system based on folic acid-targeted HBP-modified mesoporous silica nanoparticles for cancer therapy. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 590, 124470.

    Article  Google Scholar 

  19. de Oliveira Silva, J., et al. (2019). Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model. Biomedicine & Pharmacotherapy, 118, 109323.

    Article  Google Scholar 

  20. Anirudhan, T., Mohan, M., & Rajeev, M. (2022). Modified chitosan-hyaluronic acid based hydrogel for the pH-responsive Co-delivery of cisplatin and doxorubicin. International Journal of Biological Macromolecules, 201, 378–388.

    Article  Google Scholar 

  21. Fathi, M., Alami-Milani, M., Geranmayeh, M. H., Barar, J., Erfan-Niya, H., & Omidi, Y. (2019). Dual thermo-and pH-sensitive injectable hydrogels of chitosan/(poly (N-isopropylacrylamide-co-itaconic acid)) for doxorubicin delivery in breast cancer. International Journal of Biological Macromolecules, 128, 957–964.

    Article  Google Scholar 

  22. Chen, W., Li, Y., Yang, S., Yue, L., Jiang, Q., & Xia, W. (2015). Synthesis and antioxidant properties of chitosan and carboxymethyl chitosan-stabilized selenium nanoparticles. Carbohydrate Polymers, 132, 574–581.

    Article  Google Scholar 

  23. Yu, S., et al. (2021). Hyaluronic acid coating on the surface of curcumin-loaded ZIF-8 nanoparticles for improved breast cancer therapy: An in vitro and in vivo study. Colloids and Surfaces B: Biointerfaces, 203, 111759.

    Article  Google Scholar 

  24. Qin, Y.-T., Peng, H., He, X.-W., Li, W.-Y., & Zhang, Y.-K. (2019). pH-responsive polymer-stabilized ZIF-8 nanocomposites for fluorescence and magnetic resonance dual-modal imaging-guided chemo-/photodynamic combinational cancer therapy. ACS Applied Materials & Interfaces, 11(37), 34268–34281.

    Article  Google Scholar 

  25. Hashemi-Moghaddam, H., Kazemi-Bagsangani, S., Jamili, M., & Zavareh, S. (2016). Evaluation of magnetic nanoparticles coated by 5-fluorouracil imprinted polymer for controlled drug delivery in mouse breast cancer model. International Journal of Pharmaceutics, 497(1–2), 228–238.

    Article  Google Scholar 

  26. Yilmaz, M. T., Ispirli, H., Taylan, O., & Dertli, E. (2021). A green nano-biosynthesis of selenium nanoparticles with Tarragon extract: Structural, thermal, and antimicrobial characterization. Lwt, 141, 110969.

    Article  Google Scholar 

  27. Chen, W., Yue, L., Jiang, Q., Liu, X., & Xia, W. (2018). Synthesis of varisized chitosan-selenium nanocomposites through heating treatment and evaluation of their antioxidant properties. International Journal Biological Macromolecules, 114, 751–758.

    Article  Google Scholar 

  28. Li, Q., Chen, J., Luo, S., Xu, J., Huang, Q., & Liu, T. (2015). Synthesis and assessment of the antioxidant and antitumor properties of asymmetric curcumin analogues. European Journal of Medicinal Chemistry, 93, 461–469.

    Article  Google Scholar 

  29. Gao, X., Zhang, J., & Zhang, L. (2002). Hollow sphere selenium nanoparticles: Their in-vitro anti hydroxyl radical effect. Advanced Materials, 14(4), 290–293.

    Article  Google Scholar 

  30. Dumore, N. S., & Mukhopadhyay, M. (2020). Antioxidant properties of aqueous selenium nanoparticles (ASeNPs) and its catalysts activity for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) reduction. Journal of Molecular Structure, 1205, 127637.

    Article  Google Scholar 

  31. Zhang, Y., Wang, J., & Zhang, L. (2010). Creation of highly stable selenium nanoparticles capped with hyperbranched polysaccharide in water. Langmuir, 26(22), 17617–17623.

    Article  Google Scholar 

  32. Bahrami, B., et al. (2017). Nanoparticles and targeted drug delivery in cancer therapy. Immunology Letters, 190, 64–83. https://doi.org/10.1016/j.imlet.2017.07.015

    Article  Google Scholar 

  33. Zhang, C., Zhai, X., Zhao, G., Ren, F., & Leng, X. (2015). Synthesis, characterization, and controlled release of selenium nanoparticles stabilized by chitosan of different molecular weights. Carbohydrate Polymers, 134, 158–166.

    Article  Google Scholar 

  34. Song, P., Lu, Z., Jiang, T., Han, W., Chen, X., & Zhao, X. (2022). Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1. International Journal of Biological Macromolecules, 222, 1078–1091. https://doi.org/10.1016/j.ijbiomac.2022.09.245

    Article  Google Scholar 

  35. Adimoolam, M. G., Amreddy, N., Nalam, M. R., & Sunkara, M. V. (2018). A simple approach to design chitosan functionalized Fe3O4 nanoparticles for pH responsive delivery of doxorubicin for cancer therapy. Journal of Magnetism and Magnetic Materials, 448, 199–207. https://doi.org/10.1016/j.jmmm.2017.09.018

    Article  Google Scholar 

  36. Karimifard, S., et al. (2022). pH-Responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Applied Nano Materials, 5(7), 8811–8825. https://doi.org/10.1021/acsanm.2c00861

    Article  Google Scholar 

  37. Unsoy, G., Khodadust, R., Yalcin, S., Mutlu, P., & Gunduz, U. (2014). Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery. European Journal of Pharmaceutical Sciences, 62, 243–250.

    Article  Google Scholar 

  38. Nogueira, D. R., Tavano, L., Mitjans, M., Pérez, L., Infante, M. R., & Vinardell, M. P. (2013). In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles. Biomaterials, 34(11), 2758–2772.

    Article  Google Scholar 

  39. Unsoy, G., Yalcin, S., Khodadust, R., Mutlu, P., Onguru, O., & Gunduz, U. (2014). Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy. Biomedicine & Pharmacotherapy, 68(5), 641–648.

    Article  Google Scholar 

  40. Lotfi, S., Bahari, A., & Mahjoub, S. (2019). In vitro biological evaluations of Fe3O4 compared with core–shell structures of chitosan-coated Fe3O4 and polyacrylic acid-coated Fe3O4 nanoparticles. Research on Chemical Intermediates, 45(6), 3497–3512. https://doi.org/10.1007/s11164-019-03804-5

    Article  Google Scholar 

  41. Ferreira, L. M., et al. (2015). Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration. Colloids and Surfaces B: Biointerfaces, 130, 272–277.

    Article  Google Scholar 

  42. Nurgali, K., Jagoe, R. T., & Abalo, R. (2018). Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? Frontiers in Pharmacology, 9, 245.

    Article  Google Scholar 

  43. Chen, Q., et al. (2022). Dual-pH responsive chitosan nanoparticles for improving in vivo drugs delivery and chemoresistance in breast cancer. Carbohydrate Polymers, 290, 119518.

    Article  Google Scholar 

  44. Menon, S., Ks, S. D., Santhiya, R., Rajeshkumar, S., & Kumar, V. (2018). Selenium nanoparticles: A potent chemotherapeutic agent and an elucidation of its mechanism. Colloids and Surfaces B: Biointerfaces, 170, 280–292.

    Article  Google Scholar 

  45. Shakibaie, M., Shahverdi, A. R., Faramarzi, M. A., Hassanzadeh, G. R., Rahimi, H. R., & Sabzevari, O. (2013). Acute and subacute toxicity of novel biogenic selenium nanoparticles in mice. Pharmaceutical Biology, 51(1), 58–63.

    Article  Google Scholar 

  46. Gangadoo, S., Stanley, D., Hughes, R. J., Moore, R. J., & Chapman, J. (2017). The synthesis and characterisation of highly stable and reproducible selenium nanoparticles. Inorganic and Nano-Metal Chemistry, 47(11), 1568–1576.

    Article  Google Scholar 

  47. Lin, Z., et al. (2017). Inhibition of H1N1 influenza virus by selenium nanoparticles loaded with zanamivir through p38 and JNK signaling pathways. RSC Advances, 7(56), 35290–35296.

    Article  Google Scholar 

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Acknowledgements

All procedures were conducted according to the Ethical Guidelines for Research, Zanjan University of Medical Sciences University, Zanjan, Iran (Ethical Codes: IR.ZUMS.REC.1399.343 and IR.ZUMS.AEC.1402.029). This research was financially supported by Zanjan University of Medical Sciences, Zanjan, Iran (Grant No: A-12-1381-3) and Trita Nanomedicine Research & Technology Development Center (TNRTC).

Funding

This research was financially supported by Zanjan University of Medical Sciences, Zanjan, Iran (Grant No: A-12–1381-3) and Trita Nanomedicine Research & Technology Development Center (TNRTC).

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Authors and Affiliations

  1. Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, 45139-56184, Iran

    Zahra Karami, Erfan Aghajani, Maryam Salami, Nasim Shadmani, Zahra Khalili, Mehrdad Hamidi, Maryam Masoumshahi & Masumeh Kurd

  2. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

    Zahra Karami & Mehrdad Hamidi

  3. Trita Nanomedicine Research & Technology Development Center (TNRTC), Zanjan Health Technology Park, Zanjan, Iran

    Nasim Shadmani, Mehrdad Hamidi & Masumeh Kurd

  4. Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran

    Fatemeh Saghatchi Zanjani

  5. Department of Pharmaceutics, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran

    Saeed Ghanbarzadeh

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  1. Zahra Karami
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Contributions

The authors confirm their contribution to the paper as follows: study conception and design: Z.K., M.H., S.G.; data collection: E.A., N.S., M.S., Z.K., M.M; analysis and interpretation of results: Z.K., M.H.; draft manuscript preparation: Z.K., F.S.Z., M.K. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Zahra Karami.

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All procedures were conducted according to the Ethical Guidelines for Research, Zanjan University of Medical Sciences University, Zanjan, Iran (Ethical Codes: IR.ZUMS.REC.1399.343 and IR.ZUMS.AEC.1402.029).

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Karami, Z., Aghajani, E., Salami, M. et al. Enhanced Antitumor and Antimetastatic Activity of pH-Responsive Curcumin-Loaded Chitosan-Selenium Nanocomposites against Breast Cancer. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01431-y

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