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TiO2 hollow nanospheres functionalized with folic acid and ZnPc for targeted photodynamic therapy in glioblastoma cancer

Abstract

Glioblastoma (GBM) is one of the most aggressive types of cancer which currently does not have a cure. Its invasive nature and heterogeneity makes its complete surgical removal impossible. Hence, a targeted treatment is critically needed to effectively eradicate this cancer. In this work, the authors report the synthesis of hollow TiO2 nanospheres (HTiO2NS) and their functionalization with folic acid (FA) and zinc (II) tet-ranitrophthalocyanine (ZnPc) to achieve cell selectivity and light absorption in the visible range. In vitro cytotoxicity of the functionalized HTiO2NS against M059K cell line (Human GBM cancer cells) was tested. In vitro generation of reactive oxygen species by HTiO2NS–FA–ZnPc nano-structures under UV irradiation was detected by fluorescence probing. To identify HTiO2NS–FA–ZnPc cell localization, the nanoparticles were labeled with fluorescein isothiocyanate dye and visualized by fluorescence microscopy. Results illustrate that HTiO2NS–FA–ZnPc nanostructures have the potential to be used for targeted photodynamic therapy for the treatment of GBM cancer.

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References

  1. 1.

    P.Y. Wen and S. Kesari: Malignant gliomas in adults. N. Engl. J. Med. 359, 492–507 (2008).

    CAS  Article  Google Scholar 

  2. 2.

    D.E. Dolmans, D. Fukumura, and R.K. Jain: Photodynamic therapy for cancer. Nat. Rev. Cancer 3, 380–387 (2003).

    CAS  Article  Google Scholar 

  3. 3.

    T.J. Dougherty, C.J. Gomer, B.W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, and Q. Peng: Photodynamic therapy. J. Natl. Cancer Inst. 90, 889–905 (1998).

    CAS  Article  Google Scholar 

  4. 4.

    J.M. Dabrowski and L.G. Arnaut: Photodynamic therapy (PDT) of cancer: from local to systemic treatment. Photochem. Photobiol. Sci. 14, 1765–1780 (2015).

    CAS  Article  Google Scholar 

  5. 5.

    T. Tachikawa, M. Fujitsuka, and T. Majima: Mechanistic insight into the TiO2 photocatalytic reactions: design of new photocatalysts. J. Phys. Chem. C 111, 5259–5275 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    C. Chawengkijwanich and Y. Hayata: Development of TiO2 powder-coated food packaging film and its ability to inactivate Escherichia coli in vitro and in actual tests. Int. J. Food Microbiol. 123, 288–292 (2008).

    CAS  Article  Google Scholar 

  7. 7.

    Z.F. Yin, L. Wu, H.G. Yang, and Y.H. Su: Recent progress in biomedical applications of titanium dioxide. Phys. Chem. Chem. Phys. 15, 4844–4858 (2013).

    Article  Google Scholar 

  8. 8.

    M. Kulkarni, A. Mazare, E. Gongadze, Š Perutkova, V. Kralj-Iglic, I. Milošev, P. Schmuki, A. Iglic, and M. Mozetic: Titanium nanostructures for biomedical applications. Nanotechnology 26, 062002 (2015).

    CAS  Article  Google Scholar 

  9. 9.

    R. Cai, Y. Kubota, T. Shuin, H. Sakai, K. Hashimoto, and A. Fujishima: Induction of cytotoxicity by photoexcited TiO2 particles. Cancer Res. 52, 2346–2348 (1992).

    CAS  Google Scholar 

  10. 10.

    G. Yang, D. Yang, P. Yang, R. Lv, C. Li, C. Zhong, F. He, S. Gai, and J. Lin: A single 808 nm near-infrared light-mediated multiple imaging and pho-todynamic therapy based on titania coupled upconversion nanoparticles. Chem. Mater. 27, 7957–7968 (2015).

    CAS  Article  Google Scholar 

  11. 11.

    X. Chen and S.S. Mao: Titanium dioxide nanomaterials: synthesis, properties, modifications, and applications. Chem. Rev. 107, 2891–2959 (2007).

    CAS  Article  Google Scholar 

  12. 12.

    R. Imani, R. Dillert, D.W. Bahnemann, M. Pazoki, T. Apih, V. Kononenko, and A. Iglic: Multifunctional gadolinium-doped mesoporous TiO2 nano-beads: photoluminescence, enhanced spin relaxation, and reactive oxygen species photogeneration, beneficial for cancer diagnosis and treatment. Small 13, 1700349 (2017).

    Article  Google Scholar 

  13. 13.

    J. Schneider, M. Matsuoka, M. Takeuchi, J. Zhang, Y. Horiuchi, M. Anpo, and D.W. Bahnemann: Understanding TiO2 photocatalysis: mechanisms and materials. Chem. Rev. 114, 9919–9986 (2014).

    CAS  Article  Google Scholar 

  14. 14.

    Z. Ji, X. Jin, S. George, T. Xia, H. Meng, X. Wang, and J.I. Zink: Dispersion and stability optimization of TiO2 nanoparticles in cell culture media. Environ. Sci. Technol. 44, 7309–7314 (2010).

    CAS  Article  Google Scholar 

  15. 15.

    T. Leshuk, S. Linley, G. Baxter, and F. Gu: Mesoporous hollow sphere titanium dioxide photocatalysts through hydrothermal silica etching. ACS Appl. Mater. Interfaces 4, 6062–6070 (2012).

    CAS  Article  Google Scholar 

  16. 16.

    K. Yu, M. Ling, J. Liang, and C. Liang: Formation of TiO2 hollow spheres through nanoscale Kirkendall effect and their lithium storage and photo-catalytic properties. Chem. Phys. 517, 222–227 (2019).

    CAS  Article  Google Scholar 

  17. 17.

    D. Liu and Y.-G. Bi: Controllable fabrication of hollow TiO2 spheres as sustained release drug carrier. Adv. Powder Technol. 30, 2169–2177 (2019).

    CAS  Article  Google Scholar 

  18. 18.

    Y.G. Assaraf, C.P. Leamon, and J.A. Reddy: The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resist. Updat. 17, 89–95 (2014).

    Article  Google Scholar 

  19. 19.

    Ł. Lamch, J. Kulbacka, M. Dubinska-Magiera, J. Saczko, and K.A. Wilk: Folate-directed zinc (II) phthalocyanine loaded polymeric micelles engineered to generate reactive oxygen species for efficacious photodynamic therapy of cancer. Photodiagnosis Photodyn. Ther. 25, 480–491 (2019).

    CAS  Article  Google Scholar 

  20. 20.

    L. Feng, C. Wang, C. Li, S. Gai, F. He, R. Li, G. An, C. Zhong, Y. Dai, Z. Yang, and P. Yang: Multifunctional theranostic nanoplatform based on Fe-mTa2O5@CuS-ZnPc/PCM for bimodal imaging and synergistically enhanced phototherapy. Inorg. Chem. 57, 4864–4876 (2018).

    CAS  Article  Google Scholar 

  21. 21.

    X. Li, B.-D. Zheng, X.-H. Peng, S.-Z. Li, J.-W. Ying, Y. Zhao, J.-D. Huang, and J. Yoon: Phthalocyanines as medicinal photosensitizers: developments in the last five years. Coord. Chem. Rev. 379, 147–160 (2019).

    CAS  Article  Google Scholar 

  22. 22.

    Z. Wang, S. Gai, C. Wang, G. Yang, C. Zhong, Y. Dai, F. He, D. Yang, and P. Yang: Self-assembled zinc phthalocyanine nanoparticles as excellent photothermal/photodynamic synergistic agent for antitumor treatment. Chem. Eng. J. 361, 117–128 (2019).

    CAS  Article  Google Scholar 

  23. 23.

    T. Lopez, E. Ortiz, M. Alvarez, J. Navarrete, J.A. Odriozola, F. Martinez-Ortega, E.A. Páez-Mozo, P. Escobar, K.A. Espinoza, and I.A. Rivero: Study of the stabilization of zinc phthalocyanine in sol-gel TiO2 for photodynamic therapy applications. Nanomedicine 6, 777–785 (2010).

    CAS  Article  Google Scholar 

  24. 24.

    Y. Shin, L. Wang, I. Bae, B.W. Arey, and G.J. Exarhos: Hydrothermal syntheses of colloidal carbon spheres from cyclodextrins. J. Phys. Chem. C 112, 14236–14240 (2008).

    CAS  Article  Google Scholar 

  25. 25.

    B. Réti, G.I. Kiss, T. Gyulavári, K. Baan, K. Magyari, and K. Hernadi: Carbon sphere templates for TiO2 hollow structures: preparation, characterization and photocatalytic activity. Catal. Today 284, 160–168 (2017).

    Article  Google Scholar 

  26. 26.

    H. Kalita, S. Konar, S. Tantubay, M.K. Mahto, and A. Pathak: Phase transformation in Mn-doped titania hollow spheres and their biocompatibility studies. Appl. Nanosci. 5, 901–910 (2015).

    CAS  Article  Google Scholar 

  27. 27.

    D. Flak, L. Yate, G. Nowaczyk, and S. Jurga: Hybrid ZnPc@TiO2 nano-structures for targeted photodynamic therapy, bioimaging and doxorubi-cin delivery. Mater. Sci. Eng. C 78, 1072–1085 (2017).

    CAS  Article  Google Scholar 

  28. 28.

    J. van Meerloo, G.J.L. Kaspers, and J. Cloos: Cell sensitivity assays: the MTT assay. Methods Mol. Biol. 731, 237–245 (2011).

    Article  Google Scholar 

  29. 29.

    T. Luttrell, S. Halpegamage, J. Tao, A. Kramer, E. Sutter, and M. Batzill: Why is anatase a better photocatalyst than rutile? - Model studies on epitaxial TiO2 films. Sci. Rep. 4, 4043 (2014).

    Article  Google Scholar 

  30. 30.

    J. Zhang, S. Rana, R.S. Srivastava, and R.D.K. Misra: On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles. Acta Biomater. 4, 40–48 (2008).

    CAS  Article  Google Scholar 

  31. 31.

    S. Shimizu and N. Kobayashi: Recent advances in the chemistry of phtha-locyanines as functional chromophores. In Chemical Science of π-Electron Systems, edited by T. Akasaka, A. Osuka, S. Fukuzumi, H. Kandori, and Y. Aso (Springer, Tokyo, 2015) pp. 273–291.

    Chapter  Google Scholar 

  32. 32.

    A.E.H. Machado, M.D. França, V. Velani, G.A. Magnino, H.M.M. Velani, F. S. Freitas, P.S. Müller Jr., C. Sattler, and M. Schmücker: Characterization and evaluation of the efficiency of TiO2/zinc phthalocyanine nanocompo-sites as photocatalysts for wastewater treatment using solar irradiation. Int. J. Photoenergy 2008, 482373 (2008).

    Article  Google Scholar 

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Acknowledgments

This material is based upon work supported by a grant from the University of California Institute for Mexico and the United States (UC MEXUS) and the Consejo Nacional de Ciencia y Tecnologia de Mexico (CONACYT; UCR-17091220).

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Correspondence to Alfredo A. Martinez-Morales.

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Supplementary material

The supplementary material for this article can be found at u]https://doi.org/10.1557/mrc.2019.142.

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Uribe-Robles, M., Ortiz-Islas, E., Rodriguez-Perez, E. et al. TiO2 hollow nanospheres functionalized with folic acid and ZnPc for targeted photodynamic therapy in glioblastoma cancer. MRS Communications 9, 1242–1248 (2019). https://doi.org/10.1557/mrc.2019.142

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