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Novel Chemo-Photothermal Therapy in Hepatic Cancer Using Gemcitabine-Loaded Hyaluronic Acid Conjugated MoS2/ZnO Nanocomposites

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Abstract

Hepatocellular carcinoma is a serious illness with a high rate of mortality. A high dose of theranostic drugs with efficient diagnostic and therapeutic capabilities should be required. Chemo-photothermal therapy is presently recognized as a secure method of cancer treatment that specifically targets tumour tissue or cells. Additionally, the success of cancer therapy is increased by the use of targeted nanoparticles. The current study aims to investigate the interaction between phototherapy and the anti-hepatocellular carcinoma treatment combination HA-GEM-MoS2/ZnO nanocomposites (NCs) loaded with gemcitabine and molybdenum disulphide. NCs were synthesized and characterized using FT-IR, XRD, TEM, and DLS analyses. The present investigation shows that the synthesized HA-MoS2/ZnO nanocomposites were elongated spherical in shape and their sizes ranged from 62.3 to 75.7 nm according to the estimation using XRD results, which is consistent with TEM findings. Further, HA-MoS2/ZnO nanocomposites could effectively encapsulate the GEM, showing dual pH and thermal triggered drug release behaviour. The result of cell uptake tests clearly demonstrated improved cellular uptake of synthesized nanocomposites following HA and GEM-loaded NCs in hepatocellular carcinoma cell lines. In addition, combination therapies caused the highest incidence of cell death in hepatocellular carcinoma, according to cytotoxicity experiments and showed a good compatibility. In vitro studies prove that HA-GEM-MoS2/ZnO nanocomposites enhanced tumour treatment that combines chemotherapy and photothermal therapy to remove the tumour and prevent relapses. Still, no studies have been done to see if gemcitabine-encapsulated HA-MoS2/ZnO NCs inhibit human hepatocellular carcinoma cell. Hence, the current study can give a new paradigm for the diagnosis and treatment of cancer and the outcome may be helpful to improve the quality of cancer patient’s life.

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References

  1. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394–424.

    PubMed  Google Scholar 

  2. Vetrivel, C., Sivarasan, G., Durairaj, K., Ragavendran, C., Kamaraj, C., Karthika, S., & Lo, H. M. (2023). MoS2-ZnO nanocomposite mediated immunosensor for non-invasive electrochemical detection of IL8 oral tumor biomarker. Diagnostics, 13, 1464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., Stein, K. D., Alteri, R., & Jemal, A. (2016). Cancer treatment and survivorship statistics. CA: A Cancer Journal for Clinicians, 66(4), 271–289.

    PubMed  Google Scholar 

  4. Bhirde, A. A., Chikkaveeraiah, B. V., Avinash, S., Gang, N., Jin, A. J., Ankur, K., Zhe, W., Sachin, P., Vyomesh, P., & Gorbach, A. M. (2014). Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance. ACS Nano, 8, 4177–4189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sherlock, S. P., Tabakman, S. M., Xie, L., & Dai, H. (2011). Photothermally enhanced drug delivery by ultrasmall multifunctional FeCo/graphitic-shell nanocrystals. ACS Nano, 5, 1505–1512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Liu, H., Chen, D., Li, L., Liu, T., Tan, L., Wu, X., & Tang, F. (2011). Multifunctional gold nanoshells on silica nanorattles: A platform for the combination of photothermal therapy and chemotherapy with low systemic toxicity. Angewandte Chemie International Edition, 50, 891–895.

    Article  CAS  PubMed  Google Scholar 

  7. Yanbo, Y., Jianrong, W., David, H. B., Shiwei, N., YuLi, X. Z., Xiaotian, X., & Li-Min, Z. (2020). A multifunctional nanoplatform based on MoS2-nanosheets for targeted drug delivery and chemo-photothermal therapy. Colloids and Surfaces B: Biointerfaces, 185, 110585.

    Article  Google Scholar 

  8. Gaofeng, S., Minjiang, C., Jingjing, S., Xiaoling, X., Chenying, L., Yuyin, D., Min, X., Zhongwei, Z., Minxia, Z., Kai, F., Xiaoxi, F., Shiji, F., Bufu, T. D., Yongzhong, D., & Jiansong, J. (2021). Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+ as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer. Bioactive Materials, 6, 1423–1435.

    Article  Google Scholar 

  9. Lv, R., Yang, D., Yang, P., Xu, J., He, F., Gai, S., Li, C., Dai, Y., Yang, G., & Lin, J. (2016). Integration of upconversion nanoparticles and ultrathin black phosphorus for efficient photodynamic theranostics under 808 nm near-infrared light irradiation. Chemistry of Materials, 28(13), 4724–4734.

    Article  CAS  Google Scholar 

  10. Nandi, S., Bhunia, S. K., Zeiri, L., Pour, M., Nachman, I., Raichman, D., Lellouche, J. M., & Jelinek, R. (2017). Bifunctional carbon-dot-WS2 nanorods for photothermal therapy and cell imaging. Chemistry, 23(4), 963–969.

    Article  CAS  PubMed  Google Scholar 

  11. Li, D., Meng, Z., Fan, Xu., Yingzhi, C., Binfan, C., Ya, C., Huihai, Z., Hongyue, J., & Yongzhuo, H. (2018). Biomimetic albumin-modified gold nanorods for photothermo-chemotherapy and macrophage polarization modulation. Acta Pharmaceutica Sinica B, 8(1), 74–84.

    Article  PubMed  Google Scholar 

  12. Shun, S., Hongyan, T., Xiaotong, Z., Jinfeng, R., Zhiqing, P., Dangge, W., Huile, G., Yong, Q., & Xinguo, J. (2013). Targeting mesoporous silica-encapsulated gold nanorods for chemo- photothermal therapy with near-infrared radiation. Biomaterials, 34(12), 3150–3158.

    Article  Google Scholar 

  13. Reza, A., Seyed, H. R., Mohammad, R. Y., Roya, S., & Effat, A. (2020). Novel chemo-photothermal therapy in breast cancer using methotrexate-loaded folic acid conjugated Au@SiO 2 nanoparticles. Nanoscale Research Letters, 15, 62.

    Article  Google Scholar 

  14. Vimala, K., Shanthi, K., Sundarraj, S., & Kannan, K. (2017). Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet. Journal of Colloid and Interface Science., 488, 92–108.

    Article  CAS  PubMed  Google Scholar 

  15. Voiry, R., Fullon, J., Yang, C. D. C. C., Silva, E., Kappera, R., Bozkurt, I., Kaplan, D., Lagos, M. J., Batson, P. E., & Gupta, G. (2016). The role of electronic coupling between substrate and 2D MoS2 nanosheets in electrocatalytic production of hydrogen. Nature Materials, 15(9), 1003.

    Article  CAS  PubMed  Google Scholar 

  16. Li, X., Shan, J., Zhang, W., Su, S., Yuwen, L., & Wang, L. (2017). Recent advances in synthesis and biomedical applications of two-dimensional transition metal dichalcogenide nanosheets. Small (Weinheim an der Bergstrasse, Germany), 13(5), 1602660.

    Article  Google Scholar 

  17. Zhang, Y., Xiu, W., Sun, Y., Zhu, D., Zhang, Q., Yuwen, L., Weng, L., Teng, Z., & Wang, L. (2017). RGD-QD-MoS 2 nanosheets for targeted fluorescent imaging and photothermal therapy of cancer. Nanoscale, 9(41), 15835–15845.

    Article  CAS  PubMed  Google Scholar 

  18. Dicker, K. T., Gurski, L. A., Pradhan-Bhatt, S., Witt, R. L., Farach-Carson, M. C., & Jia, X. (2014). Hyaluronan: A simple polysaccharide with diverse biological functions. Acta Biomaterialia, 10(4), 1558–1570.

    Article  CAS  PubMed  Google Scholar 

  19. Zhong, Y., Goltsche, K., Cheng, L., Xie, F., Meng, F., Deng, C., Zhong, Z., & Haag, R. (2016). Hyaluronic acid-shelled acid-activatable paclitaxel prodrug micelles effectively target and treat CD44-overexpressing human breast tumor xenografts in vivo. Biomaterials, 84, 250–261.

    Article  CAS  PubMed  Google Scholar 

  20. Chen, X., Liu, Z., Parker, S. G., Zhang, X., Gooding, J. J., Ru, Y., Liu, Y., & Zhou, Y. (2016). Light-induced hydrogel based on tumour-targeting mesoporous silica nanoparticles as a theranostic platform for sustained cancer treatment. ACS Applied Materials & Interfaces, 8(25), 15857–15863.

    Article  CAS  Google Scholar 

  21. Goncalves, D. P. N., Rodriguez, R. D., Kurth, T., Bray, L. J., Binner, M., Jungnickel, C., Gur, F., Poser, S. W., Schmidt, T. L., Zahn, D. R. T., Androutsellis-Theotokis, A., Schlierf, M., & Werner, C. (2017). Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D cultures. Acta Biomaterialia, 58, 12–25.

    Article  CAS  PubMed  Google Scholar 

  22. Dong, X., Yin, W., Zhang, X., Zhu, S., He, X., Yu, J., Xie, J., Guo, Z., Yan, L., Liu, X., Wang, Q., Gu, Z., & Zhao, Y. (2018). Intelligent MoS2 nanotheranostic for targeted and Enzyme-/pH-/NIR-responsive drug delivery to overcome cancer chemotherapy resistance guided by PET imaging. ACS Applied Materials & Interfaces, 10(4), 4271–4284.

    Article  CAS  Google Scholar 

  23. Krishnan, U., Kaur, M., Kaur, G., Singh, K., Dogra, A. R., Kumar, M., & Kumar, A. (2018). MoS2 /ZnO nanocomposites for efficient photocatalytic degradation of industrial pollutants. Materials Research Bulletin., 111, 212–221.

    Article  Google Scholar 

  24. Ren, Z., Han, X., Wang, L., & Wang, Y. (2022). Hyaluronic acid-functionalized ZnO nanoparticles co-deliver AS and GOD for synergistic cancer starvation and oxidative damage. Scientific Reports., 12, 4574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vimala, K., Sundarraj, S., Paulpandi, M., Vengatesan, S., & Kannan, K. (2014). Green synthesized doxorubicin loaded zinc oxide nanoparticles regulates the Bax and Bcl-2 expression in breast and colon carcinoma. Process Biochemistry, 49(1), 160–172.

    Article  CAS  Google Scholar 

  26. Xie, M., Na, Y., Jiaxi, C., Mei, Y., Tongtong, D., Yeping, L., & Chunlai, F. (2020). Layered MoS2 nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer with chemo-photothermal therapy. Colloids and Surfaces B: Biointerfaces., 187, 110631.

    Article  CAS  PubMed  Google Scholar 

  27. Chen, Y., Tan, C., Zhang, H., & Wang, L. (2015). Two-dimensional graphene analogues for biomedical applications. Chemical Society Reviews, 44(9), 2681–2701.

    Article  CAS  PubMed  Google Scholar 

  28. Liu, J., Zheng, J., Nie, H., Zhang, D., Cao, D., Xing, C., Li, B., & Jia, L. (2019). Molybdenum disulfide-based hyaluronic acid-guided multifunctional theranostic nanoplatform for magnetic resonance imaging and synergetic chemo-photothermal therapy. Journal of Colloid and Interface Science., 548, 131–144.

    Article  CAS  PubMed  Google Scholar 

  29. Cai, H., Ruobing, W., Xingren, G., Meiyu, S., Fei, Y., Bai, J., & Yahui, L. (2021). Combining gemcitabine-loaded macrophage-like nanoparticles and erlotinib for pancreatic cancer therapy. Mol. Pharmaceutics., 18, 2495–2506.

    Article  CAS  Google Scholar 

  30. Wang, S., Chen, Y., Li, X., Gao, W., Zhang, L., Liu, L., Zheng, Y., Chen, H., & Shi, J. (2015). Injectable 2D MoS2-integrated drug delivering implant for highly efficient NIR-triggered synergistic tumor hyperthermia. Advanced Materials, 27(44), 7117–7122.

    Article  CAS  PubMed  Google Scholar 

  31. Zhenkun, R., Xibin, H., Lixin, W., & Yi, W. (2022). Hyaluronic acid-functionalized ZnO nanoparticles co-deliver AS and GOD for synergistic cancer starvation and oxidative damage. Scientific Reports, 12, 4574.

    Article  Google Scholar 

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Funding

Shanghai Jinshan District Science and Technology Innovation Fund Project (No.2019-3-10).

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GW planned, designed, and wrote the original draft of this manuscript. Artwork–figures, conceptualization, and supervision were done by DY.

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Correspondence to Dong Yu.

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Wang, G., Yu, D. Novel Chemo-Photothermal Therapy in Hepatic Cancer Using Gemcitabine-Loaded Hyaluronic Acid Conjugated MoS2/ZnO Nanocomposites. Appl Biochem Biotechnol (2023). https://doi.org/10.1007/s12010-023-04796-0

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