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Novel Silymarin-Loaded Biosynthesized AgNPs for Improving Anticancer Activities in Breast Cancer

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Abstract

Plant-derived compounds with anti-cancer effects are known as new candidates for treatment. Silymarin is one of these effective compounds; however, the low solubility of silymarin in aqueous systems can be one of the possible obstacles. Nanotechnology has been used to increase the solubility of poorly water-soluble drugs. In this study, silymarin was delivered with silver nanoparticles (AgNPs) to breast cancer cells. Nanoparticles were synthesized by the green method using gallic acid. Silymarin loading into nanoparticles was confirmed by FTIR. The toxicity of AgNPs, silymarin, and AgNPs/silymarin on two different breast cancer lines (MCF7 and MDA-MB-231) and normal HDF cells was investigated. According to results, AgNPs/silymarin exhibited a greater lethal effect on cancer lines compared to single treatment and much less lethal effect on the HDF cell. Inhibition of colony formation, migration and increased apoptosis were found to be effective on the treatment with AgNPs/silymarin compared to single treatments. The highest decrease in the expression of genes involved in metastasis, KRAS, MMP2/9, and TPM3 was observed. The use of AgNPs to deliver silymarin to cancer cells creates different inhibitory mechanisms against cancer cells, which highlights the use of AgNPs as drug delivery systems in cancer.

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References

  1. Boisselier, E., & Astruc, D. (2009). Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chemical Society Reviews, 38(6), 1759–1782.

    Article  Google Scholar 

  2. Iyer, A. K., He, J., & Amiji, M. M. (2012). Image-guided nanosystems for targeted delivery in cancer therapy. Current Medicinal Chemistry, 19(19), 3230–3240.

    Article  Google Scholar 

  3. Sargazi, S., et al. (2022). Application of green gold nanoparticles in cancer therapy and diagnosis. Nanomaterials, 12(7), 1102.

    Article  Google Scholar 

  4. Holgado, M. A., Martin-Banderas, L., Alvarez-Fuentes, J., Fernandez-Arevalo, M., & Arias, J. L. (2012). Drug targeting to cancer by nanoparticles surface functionalized with special biomolecules. Current Medicinal Chemistry, 19(19), 3188–3195.

    Article  Google Scholar 

  5. Khan, M. I., et al. (2022). Recent progress in nanostructured smart drug delivery systems for cancer therapy: A review. ACS Applied Bio Materials, 5(3), 971–1012.

    Article  Google Scholar 

  6. Pradhan, S., & Girish, C. (2006). Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian Journal of Medical Research, 124(5), 491.

    Google Scholar 

  7. Manna, S. K., Mukhopadhyay, A., Van, N. T., & Aggarwal, B. B. (1999). Silymarin suppresses TNF-induced activation of NF-κB, c-Jun N-terminal kinase, and apoptosis. The Journal of Immunology, 163(12), 6800–6809.

    Article  Google Scholar 

  8. Morazzoni, P., Montalbetti, A., Malandrino, S., & Pifferi, G. (1993). Comparative pharmacokinetics of silipide and silymarin in rats. European Journal of Drug Metabolism and Pharmacokinetics, 18(3), 289–297.

    Article  Google Scholar 

  9. Morais, M., Teixeira, A. L., Dias, F., Machado, V., Medeiros, R., & Prior, J. A. (2020). Cytotoxic effect of silver nanoparticles synthesized by green methods in cancer. Journal of Medicinal Chemistry, 63(23), 14308–14335.

    Article  Google Scholar 

  10. Gomes, H. I., Martins, C. S., & Prior, J. A. (2021). Silver nanoparticles as carriers of anticancer drugs for efficient target treatment of cancer cells. Nanomaterials, 11(4), 964.

    Article  Google Scholar 

  11. Barabadi, H., Ovais, M., Shinwari, Z. K., & Saravanan, M. (2017). Anti-cancer green bionanomaterials: Present status and future prospects. Green Chemistry Letters and Reviews, 10(4), 285–314.

    Article  Google Scholar 

  12. Das, R. K., et al. (2017). Biological synthesis of metallic nanoparticles: plants, animals and microbial aspects. Nanotechnology for Environmental Engineering, 2(1), 1–21.

    Article  MathSciNet  Google Scholar 

  13. Cheng, N., et al. (2019). Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions. Bioscience Reports, 39(11), BSR20191511.

    Article  Google Scholar 

  14. Puttaraju, N. G., Venkateshaiah, S. U., Dharmesh, S. M., Urs, S. M. N., & Somasundaram, R. (2006). Antioxidant activity of indigenous edible mushrooms. Journal of Agricultural and Food Chemistry, 54(26), 9764–9772.

    Article  Google Scholar 

  15. Chia, Y.-C., Rajbanshi, R., Calhoun, C., & Chiu, R. H. (2010). Anti-neoplastic effects of gallic acid, a major component of Toona sinensis leaf extract, on oral squamous carcinoma cells. Molecules, 15(11), 8377–8389.

    Article  Google Scholar 

  16. Kim, Y.-J. (2007). Antimelanogenic and antioxidant properties of gallic acid. Biological and Pharmaceutical Bulletin, 30(6), 1052–1055.

    Article  Google Scholar 

  17. Kratz, J. M., et al. (2008). Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate. Memórias do Instituto Oswaldo Cruz, 103(5), 437–442.

    Article  Google Scholar 

  18. Alam, B., et al. (2013). Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves. Avicenna Journal of Phytomedicine, 3(2), 112.

    Google Scholar 

  19. Kubo, I., Fujita, K. I., Nihei, K. I., & Masuoka, N. (2003). Non-antibiotic antibacterial activity of dodecyl gallate. Bioorganic & Medicinal Chemistry, 11(4), 573–580.

    Article  Google Scholar 

  20. Kubo, I., Xiao, P., & Fujita, K. I. (2001). Antifungal activity of octyl gallate: Structural criteria and mode of action. Bioorganic & Medicinal Chemistry Letters, 11(3), 347–350.

    Article  Google Scholar 

  21. Graham, L. J., et al. (2014). Current approaches and challenges in monitoring treatment responses in breast cancer. Journal of Cancer, 5(1), 58.

    Article  Google Scholar 

  22. McAnena, P., Lowery, A., & Kerin, M. (2018). Role of micro-RNAs in breast cancer surgery. British Journal of Surgery, 105(2), e19–e30.

    Article  Google Scholar 

  23. Liu, Y., Hussain, M., Wang, X., Liu, B., & Yuan, Y. (2020). Anti-tumor activity of verbascoside-loaded noble metal nanoparticles. In Nanoparticle Drug Delivery Systems for Cancer Treatment (pp. 271–294). Jenny Stanford Publishing.

    Chapter  Google Scholar 

  24. Jaggi, A. S., & Singh, N. (2016). Silymarin and its role in chronic diseases. Drug Discovery from Mother Nature, 25–44.

  25. Amirsaadat, S., Jafari-Gharabaghlou, D., Alijani, S., Mousazadeh, H., Dadashpour, M., & Zarghami, N. (2021). Metformin and Silibinin co-loaded PLGA-PEG nanoparticles for effective combination therapy against human breast cancer cells. Journal of Drug Delivery Science and Technology, 61, 102107.

    Article  Google Scholar 

  26. Xie, Y., Zhang, D., Zhang, J., & Yuan, J. (2019). Metabolism, transport and drug–drug interactions of silymarin. Molecules, 24(20), 3693.

    Article  Google Scholar 

  27. Park, J., Cha, S.-H., Cho, S., & Park, Y. (2016). Green synthesis of gold and silver nanoparticles using gallic acid: Catalytic activity and conversion yield toward the 4-nitrophenol reduction reaction. Journal of Nanoparticle Research, 18, 1–13.

    Article  Google Scholar 

  28. Zhang, T., et al. (2019). Gallic acid has anticancer activity and enhances the anticancer effects of cisplatin in non-small cell lung cancer A549 cells via the JAK/STAT3 signaling pathway. Oncology Reports, 41(3), 1779–1788.

    Google Scholar 

  29. Jiang, Y., Pei, J., Zheng, Y., Miao, Y. J., Duan, B. Z., & Huang, L. F. (2021). Gallic acid: A potential anti-cancer agent. Chinese Journal of Integrative Medicine, 1–11.

  30. Shakeran, Z., Keyhanfar, M., Varshosaz, J., & Sutherland, D. S. (2021). Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for delivery of methotrexate for application in breast cancer treatment. Materials Science and Engineering: C, 118, 111526.

    Article  Google Scholar 

  31. Dadashpour, M., et al. (2018). Biomimetic synthesis of silver nanoparticles using Matricaria chamomilla extract and their potential anticancer activity against human lung cancer cells. Materials Science and Engineering: C, 92, 902–912.

    Article  Google Scholar 

  32. Anand, K., et al. (2016). Biosynthesis of palladium nanoparticles by using Moringa oleifera flower extract and their catalytic and biological properties. Journal of Photochemistry and Photobiology B: Biology, 165, 87–95.

    Article  Google Scholar 

  33. Kummara, S., Patil, M. B., & Uriah, T. (2016). Synthesis, characterization, biocompatible and anticancer activity of green and chemically synthesized silver nanoparticles–A comparative study. Biomedicine & Pharmacotherapy, 84, 10–21.

    Article  Google Scholar 

  34. Delmas, D., Xiao, J., Vejux, A., & Aires, V. (2020). Silymarin and cancer: A dual strategy in both in chemoprevention and chemosensitivity. Molecules, 25(9), 2009.

    Article  Google Scholar 

  35. Atawia, R. T., Tadros, M. G., Khalifa, A. E., Mosli, H. A., & Abdel-Naim, A. B. (2013). Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats. Toxicology letters, 219(2), 160–169.

    Article  Google Scholar 

  36. Koltai, T., & Fliegel, L. (2022). "Role of silymarin in cancer treatment: Facts, hypotheses, and questions," Journal of Evidence-Based. Integrative Medicine, 27, 2515690X211068826.

    Google Scholar 

  37. Ramteke, L., Gawali, P., Jadhav, B., & Chopade, B. (2020). Comparative study on antibacterial activity of metal ions, monometallic and alloy noble metal nanoparticles against nosocomial pathogens. BioNanoScience, 10(4), 1018–1036.

    Article  Google Scholar 

  38. Singh, R. P., & Ramarao, P. (2012). Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles. Toxicology Letters, 213(2), 249–259.

    Article  Google Scholar 

  39. Patra, S., Mukherjee, S., Barui, A. K., Ganguly, A., Sreedhar, B., & Patra, C. R. (2015). Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics. Materials Science and Engineering: C, 53, 298–309.

    Article  Google Scholar 

  40. Javan, E. S., Lotfi, F., Jafari-Gharabaghlou, D., Mousazadeh, H., Dadashpour, M., & Zarghami, N. (2022). Development of a magnetic nanostructure for co-delivery of metformin and silibinin on growth of lung cancer cells: Possible action through leptin gene and its receptor regulation. Asian Pacific Journal of Cancer Prevention: APJCP, 23(2), 519.

    Article  Google Scholar 

  41. Gurunathan, S., Han, J. W., Eppakayala, V., Jeyaraj, M., & Kim, J.-H. (2013). Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells. BioMed Research International, 2013, 10. https://doi.org/10.1155/2013/535796

    Article  Google Scholar 

  42. Jeyaraj, M., et al. (2013). An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using Podophyllum hexandrum on human cervical carcinoma cells. Colloids and Surfaces B: Biointerfaces, 102, 708–717.

    Article  Google Scholar 

  43. Zada, S., et al. (2018). Biogenic synthesis of silver nanoparticles using extracts of Leptolyngbya JSC-1 that induce apoptosis in HeLa cell line and exterminate pathogenic bacteria. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup3), 471–480.

    Article  Google Scholar 

  44. Khalili, H., Sadat Shandiz, S. A., & Baghbani-Arani, F. (2017). Anticancer properties of phyto-synthesized silver nanoparticles from medicinal plant Artemisia tschernieviana Besser aerial parts extract toward HT29 human colon adenocarcinoma cells. Journal of Cluster Science, 28, 1617–1636.

    Article  Google Scholar 

  45. Fan, L., Ma, Y., Liu, Y., Zheng, D., & Huang, G. (2014). Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. European Journal of Pharmacology, 743, 79–88.

    Article  Google Scholar 

  46. Kim, S. H., et al. (2019). Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncology Reports, 42(5), 1904–1914.

    Google Scholar 

  47. Hosseinabadi, T., et al. (2019). Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer. Phytotherapy Research, 33(11), 2849–2861.

    Article  Google Scholar 

  48. Pourgholi, A., Dadashpour, M., Mousapour, A., Firouzi Amandi, A., & Zarghami, N. (2021). Anticancer potential of silibinin loaded polymeric nanoparticles against breast cancer cells: Insight into the apoptotic genes targets. Asian Pacific Journal of Cancer Prevention: APJCP, 22(8), 2587–2596.

    Article  Google Scholar 

  49. Mogheri, F., et al. (2021). Co-delivery of metformin and silibinin in dual-drug loaded nanoparticles synergistically improves chemotherapy in human non-small cell lung cancer A549 cells. Journal of Drug Delivery Science and Technology, 66, 102752.

    Article  Google Scholar 

  50. Tousson, E., Salama, A. F., Dora, M. A., & Elony, M. A. (2016). Comparative cardioprotective effect of Egyptian Silybum marianum extract and Chinese silymarin in experimentally liver fibrosis. Journal of Bioscience and Applied Research, 2(2), 107–117.

    Article  Google Scholar 

  51. Chen, S., et al. (2021). TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9. Annals of Translational Medicine, 9(16).

  52. Huang, L., Guo, Z., Wang, F., & Fu, L. (2021). KRAS mutation: From undruggable to druggable in cancer. Signal Transduction and Targeted Therapy, 6(1), 386.

    Article  Google Scholar 

  53. Jiang, H., & Li, H. (2021). Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: A systematic review and meta-analysis. BMC Cancer, 21, 1–13.

    Article  Google Scholar 

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A. Masoudi Chelegahi performed most of the experiments as part of his master’s degree in Genetics. R. Heidari and B. Karimi were thesis advisors and participated in intellectual discussions of the data. S. Reiisi coordinated the study, designed the experiments, and revised the manuscript.

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Correspondence to Somayeh Reiisi.

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Chelegahi, A.M., Reiisi, S., Heidari, R. et al. Novel Silymarin-Loaded Biosynthesized AgNPs for Improving Anticancer Activities in Breast Cancer. BioNanoSci. 13, 1817–1832 (2023). https://doi.org/10.1007/s12668-023-01183-1

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