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Singlet oxygen generation by sonication using a water-soluble fullerene (C60) complex: a potential application for sonodynamic therapy

Polymer Journal volume 52, pages 1387–1394 (2020)Cite this article

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Abstract

The generation of singlet oxygen (1O2) by sonicating a water-soluble complex of fullerene/poly(2-methacryloyloxyethyl phosphorylcholine) (C60/PMPC) was investigated for sonodynamic therapy (SDT). The effect of sonication time and the solubilized concentration of water-soluble fullerene C60 on the amount of generated 1O2 was studied. Singlet oxygen sensor green was used to confirm the generation of 1O2. 1O2 was generated from C60/PMPC under ultrasonic irradiation, and the amount of 1O2 increased with increasing solubilized C60 concentration and irradiation time. In cell viability tests, after 3 h of incubation, the cell viabilities were 10 and 84% in the presence of C60/PMPC with and without sonication, respectively. This result suggests that C60/PMPC shows a sonodynamic effect, which demonstrates its potential application in SDT.

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References

  1. You Y. Chemical tools for the generation and detection of singlet oxygen. Org Biomol Chem. 2018;16:4044–60.

    CAS  PubMed  Google Scholar 

  2. Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res. 2018;37:018–0909.

    Google Scholar 

  3. Timoshenko V. Singlet oxygen generation and detection for biomedical applications. In: Baraton M-I, editor. Sensors for environment, health and security. Dordrecht: Springer; 2009. p. 295–309.

    Google Scholar 

  4. Lv W, Xia H, Zhang KY, Chen Z, Liu S, Huang W, et al. Photothermal-triggered release of singlet oxygen from an endoperoxide-containing polymeric carrier for killing cancer cells. Mater Horiz. 2017;4:1185–9.

    CAS  Google Scholar 

  5. DeRosa MC, Crutchley RJ. Photosensitized singlet oxygen and its applications. Coord Chem Rev. 2002;233-234:351–71.

    CAS  Google Scholar 

  6. Sun D, Pang X, Cheng Y, Ming J, Xiang S, Zhang C, et al. Ultrasound-switchable nanozyme augments sonodynamic therapy against multidrug-resistant bacterial infection. ACS Nano. 2020;14:2063–76.

    CAS  PubMed  Google Scholar 

  7. Harada A, Ono M, Yuba E, Kono K. Titanium dioxide nanoparticle-entrapped polyion complex micelles generate singlet oxygen in the cells by ultrasound irradiation for sonodynamic therapy. Biomater Sci. 2013;1:65–73.

    CAS  PubMed  Google Scholar 

  8. Costley D, Nesbitt H, Ternan N, Dooley J, Huang YY, Hamblin MR, et al. Sonodynamic inactivation of Gram-positive and Gram-negative bacteria using a Rose Bengal-antimicrobial peptide conjugate. Int J Antimicrob Agents. 2017;49:31–6.

    CAS  PubMed  Google Scholar 

  9. Redmond RW, Gamlin JN. A compilation of singlet oxygen yields from biologically relevant molecules. Photochem Photobiol. 1999;70:391–475.

    CAS  PubMed  Google Scholar 

  10. Fan J, Fang G, Zeng F, Wang X, Wu S. Water-dispersible fullerene aggregates as a targeted anticancer prodrug with both chemo- and photodynamic therapeutic actions. Small. 2013;9:613–21.

    CAS  PubMed  Google Scholar 

  11. Detrembleur C, Stoilova O, Bryaskova R, Debuigne A, Mouithys-Mickalad A, Jérôme R. Preparation of well-defined PVOH/C60 nanohybrids by cobalt-mediated radical polymerization of vinyl acetate. Macromol Rapid Commun. 2006;27:498–504.

    CAS  Google Scholar 

  12. Sun M, Kiourti A, Wang H, Zhao S, Zhao G, Lu X, et al. Enhanced microwave hyperthermia of cancer cells with fullerene. Mol Pharmaceutics. 2016;13:2184–92.

    CAS  Google Scholar 

  13. Wang S, Gao R, Zhou F, Selke M. Nanomaterials and singlet oxygen photosensitizers: potential applications in photodynamic therapy. J Mater Chem. 2004;14:487–93.

    CAS  Google Scholar 

  14. Guldi DM, Prato M. Excited-state properties of C60 fullerene derivatives. Acc Chem Res. 2000;33:695–703.

    CAS  PubMed  Google Scholar 

  15. Hoebeke M, Damoiseau X. Determination of the singlet oxygen quantum yield of bacteriochlorin a: a comparative study in phosphate buffer and aqueous dispersion of dimiristoyl-l-α-phosphatidylcholine liposomes. Photochem Photobio Sci. 2002;1:283–7.

    CAS  Google Scholar 

  16. Nishiyama N, Morimoto Y, Jang WD, Kataoka K. Design and development of dendrimer photosensitizer-incorporated polymeric micelles for enhanced photodynamic therapy. Adv Drug Deliv Rev. 2009;61:327–38.

    CAS  PubMed  Google Scholar 

  17. Zhao Y, Farrer NJ, Li H, Butler JS, McQuitty RJ, Habtemariam A, et al. De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex. Angew Chem Int Ed. 2013;52:13633–7.

    CAS  Google Scholar 

  18. Pan X, Wang H, Wang S, Sun X, Wang L, Wang W, et al. Sonodynamic therapy (SDT): a novel strategy for cancer nanotheranostics. Sci China Life Sci. 2018;61:415–26.

    PubMed  Google Scholar 

  19. Yumita N, Iwase Y, Imaizumi T, Sakurazawa A, Kaya Y, Nishi K, et al. Sonodynamically-induced anticancer effects by functionalized fullerenes. Anticancer Res. 2013;33:3145–51.

    CAS  PubMed  Google Scholar 

  20. Costley D, Mc Ewan C, Fowley C, McHale AP, Atchison J, Nomikou N, et al. Treating cancer with sonodynamic therapy: a review. Int J Hyperth. 2015;31:107–17.

    CAS  Google Scholar 

  21. Wan GY, Liu Y, Chen BW, Liu YY, Wang YS, Zhang N. Recent advances of sonodynamic therapy in cancer treatment. Cancer Biol Med. 2016;13:325–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Todorović Marković B, Jokanović V, Jovanović S, Kleut D, Dramićanin M, Marković Z. Surface chemical modification of fullerene by mechanochemical treatment. Appl Surf Sci. 2009;255:7537–41.

    Google Scholar 

  23. Andrievsky GV, Kosevich MV, Vovk OM, Shelkovsky VS, Vashchenko LA. On the production of an aqueous colloidal solution of fullerenes. J Chem Soc Chem Comm. 1995:1281–82.

  24. Brant JA, Labille J, Bottero J-Y, Wiesner MR. Characterizing the impact of preparation method on fullerene cluster structure and chemistry. Langmuir. 2006;22:3878–85.

    CAS  PubMed  Google Scholar 

  25. Dhawan A, Taurozzi JS, Pandey AK, Shan W, Miller SM, Hashsham SA, et al. Stable colloidal dispersions of C60 fullerenes in water: evidence for genotoxicity. Environ Sci Technol. 2006;40:7394–401.

    CAS  PubMed  Google Scholar 

  26. Hungerbuehler H, Guldi DM, Asmus KD. Incorporation of C60 into artificial lipid membranes. J Am Chem Soc. 1993;115:3386–7.

    CAS  Google Scholar 

  27. Andersson T, Nilsson K, Sundahl M, Westman G, Wennerström O. C60 embedded in γ-cyclodextrin: a water-soluble fullerene. J Chem Soc Chem Commun. 1992;8:604–6.

    Google Scholar 

  28. Yamakoshi YN, Yagami T, Fukuhara K, Sueyoshi S, Miyata N. Solubilization of fullerenes into water with polyvinylpyrrolidone applicable to biological tests. J Chem Soc Chem Commun. 1994:517–8.

  29. Ohata T, Ishihara K, Iwasaki Y, Sangsuwan A, Fujii S, Sakurai K, et al. Water-soluble complex formation of fullerenes with a biocompatible polymer. Polym J. 2016;48:999–1005.

    CAS  Google Scholar 

  30. Lee AR. Phospholipid polymer, 2-methacryloyloxyethyl phosphorylcholine and its skin barrier function. Arch Pharm Res. 2004;27:1177–82.

    CAS  PubMed  Google Scholar 

  31. Iwasaki Y, Ishihara K. Cell membrane-inspired phospholipid polymers for developing medical devices with excellent biointerfaces. Sci Technol Adv Mater. 2012;13:1468–6996.

    Google Scholar 

  32. Yudasaka M, Yomogida Y, Zhang M, Tanaka T, Nakahara M, Kobayashi N, et al. Near-infrared photoluminescent carbon nanotubes for imaging of brown fat. Sci Rep. 2017;7:44760.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu FM, Xu JP, Ji J, Shen JC. A novel biomimetic polymer as amphiphilic surfactant for soluble and biocompatible carbon nanotubes (CNTs). Colloids Surf B Biointerfaces. 2008;67:67–72.

    CAS  PubMed  Google Scholar 

  34. Ishihara K. Blood-compatible surfaces with phosphorylcholine-based polymers for cardiovascular medical devices. Langmuir. 2019;35:1778–87.

    CAS  PubMed  Google Scholar 

  35. Ishihara K, Mu M, Konno T. Water-soluble and amphiphilic phospholipid copolymers having 2-methacryloyloxyethyl phosphorylcholine units for the solubilization of bioactive compounds. J Biomater Sci Polym Ed. 2018;29:844–62.

    CAS  PubMed  Google Scholar 

  36. Ishihara K. Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine polymers as biomaterials. J Biomed Mater Res Part A. 2019;107A:933–43.

    Google Scholar 

  37. Gollmer A, Arnbjerg J, Blaikie FH, Pedersen BW, Breitenbach T, Daasbjerg K, et al. Singlet Oxygen Sensor Green®: photochemical behavior in solution and in a mammalian cell. Photochem Photobiol. 2011;87:671–9.

    CAS  PubMed  Google Scholar 

  38. Mitsukami Y, Donovan MS, Lowe AB, McCormick CL. Water-soluble polymers. 81. Direct synthesis of hydrophilic styrenic-based homopolymers and block copolymers in aqueous solution via RAFT. Macromolecules. 2001;34:2248–56.

    CAS  Google Scholar 

  39. Takahashi T, Kono K, Itoh T, Emi N, Takagishi T. Synthesis of novel cationic lipids having polyamidoamine dendrons and their transfection activity. Bioconjugate Chem. 2003;14:764–73.

    CAS  Google Scholar 

  40. Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6:815–23.

    CAS  PubMed  Google Scholar 

  41. Adolphi U, Kulicke W-M. Coil dimensions and conformation of macromolecules in aqueous media from flow field-flow fractionation/multi-angle laser light scattering illustrated by studies on pullulan. Polymer. 1997;38:1513–9.

    CAS  Google Scholar 

  42. Bruns W. The second osmotic virial coefficient of polymer solutions. Macromolecules. 1996;29:2641–3.

    CAS  Google Scholar 

  43. Matsuda Y, Kobayashi M, Annaka M, Ishihara K, Takahara A. Dimensions of a free linear polymer and polymer immobilized on silica nanoparticles of a zwitterionic polymer in aqueous solutions with various ionic strengths. Langmuir. 2008;24:8772–8.

    CAS  PubMed  Google Scholar 

  44. Giacomelli C, Le Men L, Borsali R, Lai-Kee-Him J, Brisson A, Armes SP, et al. Phosphorylcholine-based pH-responsive diblock copolymer micelles as drug delivery vehicles: light scattering, electron microscopy, and fluorescence experiments. Biomacromolecules. 2006;7:817–28.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by a Grant-in-Aid for Scientific Research (17H03071) from the Japan Society for the Promotion of Science (JSPS), the JSPS Bilateral Joint Research Projects (JPJSBP120203509), and the Cooperative Research Program of “Network Joint Research Center for Materials and Devices” (20204034).

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Authors and Affiliations

  1. Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo, 671-2280, Japan

    Thi Lien Nguyen & Shin-ichi Yusa

  2. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8531, Japan

    Risa Katayama, Chie Kojima & Akikazu Matsumoto

  3. Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hingo, Bunkyo-ku, Hongo, Tokyo, 113-8656, Japan

    Kazuhiko Ishihara

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  1. Thi Lien Nguyen
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Nguyen, T.L., Katayama, R., Kojima, C. et al. Singlet oxygen generation by sonication using a water-soluble fullerene (C60) complex: a potential application for sonodynamic therapy. Polym J 52, 1387–1394 (2020). https://doi.org/10.1038/s41428-020-0390-1

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