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A novel tricationic fullerene C60 as broad-spectrum antimicrobial photosensitizer: mechanisms of action and potentiation with potassium iodide

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Abstract

A novel amphiphilic photosensitizing agent based on a tricationic fullerene C60 (DMC603+) was efficiently synthesized from its non-charged analogue MMC60. These fullerenes presented strong UV absorptions, with a broad range of less intense absorption up to 710 nm. Both compounds showed low fluorescence emission and were able to photosensitize the production of reactive oxygen species. Furthermore, photodecomposition of l-tryptophan sensitized by both fullerenes indicated an involvement of type II pathway. DMC603+ was an effective agent to produce the photodynamic inactivation (PDI) of Staphylococcus aureus, Escherichia coli and Candida albicans. Mechanistic insight indicated that the photodynamic action sensitized by DMC603+ was mainly mediated by both photoprocesses in bacteria, while a greater preponderance of the type II pathway was found in C. albicans. In presence of potassium iodide, a potentiation of PDI was observed due to the formation of reactive iodine species. Therefore, the amphiphilic DMC603+ can be used as an effective potential broad-spectrum antimicrobial photosensitizer.

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References

  1. Frieri, M., Kumar, K., & Boutin, A. (2017). Antibiotic resistance. Journal of Infection and Public Health, 10, 369–378.

    Article  PubMed  Google Scholar 

  2. Hassoun-Kheir, N., Stabholz, Y., Kreft, J.-U., de la Cruz, R., Romalde, J. L., Nesme, J., et al. (2020). Comparison of antibiotic-resistant bacteria and antibiotic resistance genes abundance in hospital and community wastewater: a systematic review. Science of the Total Environment, 743, 140804.

    Article  CAS  Google Scholar 

  3. Shankar, N., Soe, P.-M., & Tam, C. C. (2020). Prevalence and risk of acquisition of methicillin-resistant Staphylococcus aureus among households: a systematic review. International Journal of Infectious Diseases, 92, 105–113.

    Article  CAS  PubMed  Google Scholar 

  4. Dunn, S. J., Connor, C., & McNally, A. (2019). The evolution and transmission of multi-drug resistant Escherichia coli and Klebsiella pneumoniae: the complexity of clones and plasmids. Current Opinion in Microbiology, 51, 51–56.

    Article  CAS  PubMed  Google Scholar 

  5. Pathakumari, B., Liang, G., & Liu, W. (2020). Immune defence to invasive fungal infections: a comprehensive review. Biomedicine & Pharmacotherapy, 130, 110550.

    Article  CAS  Google Scholar 

  6. Correia, E., Roman, D., Prieto, S., Hidalgo-Vico, R., & Alonso-Monge, J. (2019). Pla, Role of Candida albicans mating in genetic variability and adaptation to the host. Fungal Biology Reviews, 33, 180–189.

    Article  Google Scholar 

  7. Hamblin, M. R. (2018). Fullerenes as photosensitizers in photodynamic therapy: pros and cons. Photochemical & Photobiological Sciences, 17, 1515–1533.

    Article  CAS  Google Scholar 

  8. Durantini, A. M., Heredia, D. A., Durantini, J. E., & Durantini, E. N. (2018). BODIPYs to the rescue: potential applications in photodynamic inactivation. European Journal of Medicinal Chemistry, 144, 651–661.

    Article  CAS  PubMed  Google Scholar 

  9. Wang, Y.-Y., Liu, Y.-C., Sun, H., & Guo, D.-S. (2019). Type I photodynamic therapy by organic–inorganic hybrid materials: from strategies to applications. Coordination Chemistry Reviews, 395, 46–62.

    Article  CAS  Google Scholar 

  10. St Denis, T. G., Vecchio, D., Zadlo, A., Rineh, A., Sadasivam, M., Avci, P., et al. (2013). Thiocyanate potentiates antimicrobial photodynamic therapy: in situ generation of the sulfur trioxide radical anion by singlet oxygen. Free Radical Biology Medicine, 65, 800–810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kasimova, K. R., Sadasivam, M., Landi, G., Sarna, T., & Hamblin, M. R. (2014). Potentiation of photoinactivation of Gram-positive and Gram-negative bacteria mediated by six phenothiazinium dyes by addition of azide ion. Photochemical & Photobiological Sciences, 13, 1541–1548.

    Article  CAS  Google Scholar 

  12. Hamblin, M. R. (2017). Potentiation of antimicrobial photodynamic inactivation by inorganic salts. Expert Review of Anti Infective Therapy, 15, 1059–1069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hamblin, M. R., & Abrahamse, H. (2018). Inorganic salts and antimicrobial photodynamic therapy: mechanistic conundrums? Molecules, 23, 3190.

    Article  PubMed Central  Google Scholar 

  14. Huang, L., Xuan, W., Zadlo, A., Kozinska, A., Sarna, T., & Hamblin, M. R. (2018). Antimicrobial photodynamic inactivation is potentiated by the addition of selenocyanate: possible involvement of selenocyanogen? Journal of Biophotonics, 11, e201800029.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang, Y., Dai, T., Wang, M., Vecchio, D., Chiang, L. Y., & Hamblin, M. R. (2015). Potentiation of antimicrobial photodynamic inactivation mediated by a cationic fullerene by added iodide: in vitro and in vivo studies. Nanomedicine, 10, 603–614.

    Article  CAS  PubMed  Google Scholar 

  16. Gsponer, N. S., Agazzi, M. L., Spesia, M. B., & Durantini, E. N. (2016). Approaches to unravel pathways of reactive oxygen species in the photoinactivation of bacteria induced by a dicationic fulleropyrrolidinium derivative. Methods, 109, 167–174.

    Article  CAS  PubMed  Google Scholar 

  17. Agazzi, M. L., Ballatore, M. B., Reynoso, E., Quiroga, E. D., & Durantini, E. N. (2017). Synthesis, spectroscopic properties and photodynamic activity of two cationic BODIPY derivatives with application in the photoinactivation of microorganisms. European Journal of Medicinal Chemistry, 126, 110–121.

    Article  CAS  PubMed  Google Scholar 

  18. Reynoso, E., Quiroga, E. D., Agazzi, M. L., Ballatore, M. B., Bertolotti, S. G., & Durantini, E. N. (2017). Photodynamic inactivation of microorganisms sensitized by cationic BODIPY derivatives potentiated by potassium iodide. Photochemical & Photobiological Sciences, 16, 1524–1536.

    Article  CAS  Google Scholar 

  19. Huang, L., Szewczyk, G., Sarna, T., & Hamblin, M. R. (2017). Potassium iodide potentiates broad-spectrum antimicrobial photodynamic inactivation using photofrin. ACS Infectious Diseases, 3, 320–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vieira, C., Gomes, A. T. P. C., Mesquita, M. Q., Moura, N. M. M., Neves, M. G. P. M. S., Faustino, M. A. F., & Almeida, A. (2018). An insight into the potentiation effect of potassium iodide on aPDT efficacy. Frontiers Microbiology, 9, 2665.

    Article  Google Scholar 

  21. De Pinillos Bayona, M., Mroz, P., Thunshelle, C., & Hamblin, M. R. (2017). Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers. Chemical Biology Drug Design, 89, 192–206.

    Article  PubMed Central  Google Scholar 

  22. Thomas, K. G., Biju, V., George, M. V., Guldi, D. M., & Kamat, P. V. (1998). Excited-state interactions in pyrrolidinofullerenes. Journal of Physical Chemistry A, 102, 5341–5348.

    Article  CAS  Google Scholar 

  23. Guldi, D. M., & Prato, M. (2000). Excited-state properties of C60 fullerene derivatives. Accounts of Chemical Research, 33, 695–703.

    Article  CAS  PubMed  Google Scholar 

  24. Koeppe, R., & Sariciftci, N. S. (2006). Photoinduced charge and energy transfer involving fullerene derivatives. Photochemical & Photobiological Sciences, 5, 1122–1131.

    Article  CAS  Google Scholar 

  25. Spesia, M. B., Milanesio, M. E., & Durantini, E. N. (2017). Fullerene derivatives in photodynamic inactivation of microorganisms, chapter 18. In A. Ficai & A. M. Grumezescu (Eds.), Nanostructures for antimicrobial therapy (pp. 413–433). Amsterdam: Elsevier Inc.

    Chapter  Google Scholar 

  26. Sharma, S. K., Chiang, L. Y., & Hamblin, M. R. (2011). Photodynamic therapy with fullerenes in vivo: reality or a dream? Nanomedicine, 6, 1813–1825.

    Article  CAS  PubMed  Google Scholar 

  27. Spesia, M. B., Milanesio, M. E., & Durantini, E. N. (2008). Synthesis, properties and photodynamic inactivation of Escherichia coli by novel cationic fullerene C60 derivatives. European Journal of Medicinal Chemistry, 43, 853–861.

    Article  CAS  PubMed  Google Scholar 

  28. Agazzi, M. L., Spesia, M. B., Gsponer, N. S., Milanesio, M. E., & Durantini, E. N. (2015). Synthesis, spectroscopic properties and photodynamic activity of a fulleropyrrolidine bearing a basic amino group and its dicationic analog against Staphylococcus aureus. Journal of Photochemistry and Photobiology A Chemistry, 310, 171–179.

    Article  CAS  Google Scholar 

  29. Tegos, G. P., Demidova, T. N., Arcila-Lopez, D., Lee, H., Wharton, T., Gali, H., & Hamblin, M. R. (2005). Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chemistry & Biology, 12, 1127–1135.

    Article  CAS  Google Scholar 

  30. Wang, M., Maragani, S., Huang, L., Jeon, S., Canteenwala, T., Hamblin, M. R., & Chiang, L. Y. (2013). Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation. European Journal of Medicinal Chemistry, 63, 170–184.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Agazzi, M. L., Durantini, J. E., Gsponer, N. S., Durantini, A. M., Bertolotti, S. G., & Durantini, E. N. (2019). Light-harvesting antenna and proton-activated photodynamic effect of a novel BODIPY-fullerene C60 dyad as potential antimicrobial agent. ChemPhysChem, 20, 1110–1125.

    Article  CAS  PubMed  Google Scholar 

  32. Yanai, T., Tew, D. P., & Handy, N. C. (2004). A new hybrid exchange–correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chemical Physics Letters, 393, 51–57.

    Article  CAS  Google Scholar 

  33. Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4, 1–7.

    Article  Google Scholar 

  34. Ballatore, M. B., Milanesio, M. E., Fujita, H., Lindsey, J. S., & Durantini, E. N. (2020). Bacteriochlorin-bis(spermine) conjugate affords an effective photodynamic action to eradicate microorganisms. Journal of Biophotonics, 13, e201960061.

    Article  PubMed  Google Scholar 

  35. Prato, M., & Maggini, M. (1998). Fulleropyrrolidines: a family of full-fledged fullerene derivatives. Accounts of Chemical Research, 31, 519–526.

    Article  CAS  Google Scholar 

  36. Tai, C.-K., Hsieh, W.-Y., Yeh, P.-L., Chiu, H.-L., & Wang, B.-C. (2013). Photo-physical properties of N-methyl-3,4-fulleropyrrolidine and its derivatives: a DFT and TD-DFT investigation. Journal of the Chinese Chemical Society, 60, 251–260.

    Article  CAS  Google Scholar 

  37. Petsalakis, I. D., Tagmatarchis, N., & Theodorakopoulos, G. (2007). Theoretical study of fulleropyrrolidines by density functional and time-dependent density functional theory. Journal of Physical Chemistry C, 111, 14139–14149.

    Article  CAS  Google Scholar 

  38. Zhang, X., & Li, X.-D. (2014). Effect of the position of substitution on the electronic properties of nitrophenyl derivatives of fulleropyrrolidines: fundamental understanding toward raising LUMO energy of fullerene electron-acceptor. Chinese Chemical Letters, 25, 501–504.

    Article  Google Scholar 

  39. Gomes, E., & Fernandes, J. L. F. C. (2005). Lima, Fluorescence probes used for detection of reactive oxygen species. Journal of Biochemical and Biophysical Methods, 65, 45–80.

    Article  CAS  PubMed  Google Scholar 

  40. Yamakoshi, Y., Umezawa, N., Ryu, A., Arakane, K., Miyata, N., Goda, Y., et al. (2003). Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-. versus 1O2. Journal of the American Chemical Society, 125, 12803–12809.

    Article  CAS  PubMed  Google Scholar 

  41. Milanesio, M. E., Spesia, M. B., Cormick, M. P., & Durantini, E. N. (2013). Mechanistic studies on the photodynamic effect induced by a dicationic fullerene C60 derivative on Escherichia coli and Candida albicans cells. Photodiagnosis Photodynamic Therapy, 10, 320–327.

    Article  CAS  PubMed  Google Scholar 

  42. Lebedeva, N. S., Yurina, E. S., Gubarev, Y. A., Lyubimtsev, A. V., & Syrbu, S. A. (2018). Effect of irradiation spectral range on porphyrin–protein complexes. Journal of Photochemistry and Photobiology A Chemistry, 353, 299–305.

    Article  CAS  Google Scholar 

  43. Ehrenshaft, M., Deterding, L. J., & Mason, R. P. (2015). Tripping up Trp: modification of protein tryptophan residues by reactive oxygen species, modes of detection, and biological consequences. Free Radical Biology and Medicine, 89, 220–228.

    Article  CAS  PubMed  Google Scholar 

  44. Wilkinson, F., Helman, W. P., & Ross, A. B. (1995). Rate constants for the decay and reactions of the lowest electronically excited singlet state of molecular oxygen in solution. An expanded and revised compilation. Journal of Physical and Chemical Reference Data, 24, 663–1021.

    Article  CAS  Google Scholar 

  45. Smith, G. J. (1978). Photo-oxidation of tryptophan sensitized by methylene blue. Journal of the Chemical Society Faraday Transaction 2, 74, 1350–1354.

    Article  CAS  Google Scholar 

  46. Di Palma, M. A., Alvarez, M. G., Ochoa, A. L., Milanesio, M. E., & Durantini, E. N. (2013). Optimization of cellular uptake of zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine for maximal photoinactivation of Candida albicans. Fungal Biology, 117, 744–751.

    Article  PubMed  Google Scholar 

  47. Puentes, S. S., & Dunstan, M. (2018). Escherichia coli complications in pediatric critical care. Critical Care Nursing Clinics of North America, 30, 149–156.

    Article  PubMed  Google Scholar 

  48. Chong, Y., Shimoda, S., & Shimono, N. (2018). Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Infection Genetics and Evolution, 61, 185–188.

    Article  Google Scholar 

  49. Pristov, K. E., & Ghannoum, M. A. (2019). Resistance of Candida to azoles and echinocandins worldwide. Clinical Microbiology & Infection, 25, 792–798.

    Article  CAS  Google Scholar 

  50. Gsponer, N. S., Spesia, M. B., & Durantini, E. N. (2015). Effects of divalent cations, EDTA and chitosan on the uptake andphotoinactivation of Escherichia coli mediated by cationic and anionic porphyrins. Photodiagnosis and Photodynamic Therapy, 12, 67–75.

    Article  CAS  PubMed  Google Scholar 

  51. Martínez, S. R., Palacios, Y. B., Heredia, D. A., Agazzi, M. L., & Durantini, A. M. (2019). Phenotypic resistance in photodynamic inactivation unravelled at the single bacterium level. ACS Infectious Diseases, 5, 1624–1633.

    Article  PubMed  Google Scholar 

  52. Ogilby, P. R. (2010). Singlet oxygen: there is still something new under the sun, and it is better than ever. Photochemical & Photobiological Sciences, 9, 1543–1560.

    Article  CAS  Google Scholar 

  53. da Silva, E. F. F., Pedersen, B. W., Breitenbach, T., Toftegaard, R., Kuimova, M. K., Arnaut, L. G., & Ogilby, P. R. (2012). Irradiation- and sensitizer-dependent changes in the lifetime of intracellular singlet oxygen produced in a photosensitized process. The Journal of Physical Chemistry B, 116, 445–461.

    Article  PubMed  Google Scholar 

  54. Yin, R., Wang, M., Huang, Y.-Y., Landi, G., Vecchio, D., Chiang, L. Y., & Hamblin, M. R. (2015). Antimicrobial photodynamic inactivation with decacationic functionalized fullerenes: oxygen-independent photokilling in presence of azide and new mechanistic insights. Free Radical Biology and Medicine, 79, 14–27.

    Article  CAS  PubMed  Google Scholar 

  55. Schweitzer, C., & Schmidt, R. (2003). Physical mechanisms of generation and deactivation of singlet oxygen. Chemical Reviews, 103, 1685–1758.

    Article  CAS  PubMed  Google Scholar 

  56. Nitzan, Y., Shainberg, B., & Malik, Z. (1989). The mechanism of photodynamic inactivation of Staphylococcus aureus by deuteroporphyrin. Current Microbiology, 19, 265–269.

    Article  CAS  Google Scholar 

  57. Huang, Y. Y., Sharma, S. K., Yin, R., Agrawal, T., Chiang, L. Y., & Hamblin, M. R. (2014). Functionalized fullerenes in photodynamic therapy. Journal of Biomedical Nanotechnology, 10, 1918–1936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cormick, M. P., Quiroga, E. D., Bertolotti, S. G., Alvarez, M. G., & Durantini, E. N. (2011). Mechanistic insight of the photodynamic effect induced by tri- and tetra-cationic porphyrins on Candida albicans cells. Photochemical & Photobiological Sciences, 10, 1556–1561.

    Article  CAS  Google Scholar 

  59. Di Palma, M. A., Alvarez, M. G., & Durantini, E. N. (2015). Photodynamic action mechanism mediated by zinc(II) 2,9,16,23-tetrakis [4-(N-methylpyridyloxy)]phthalocyanine in Candida albicans cells. Photochemistry and Photobiology, 91, 1203–1209.

    Article  PubMed  Google Scholar 

  60. Felgenträger, T., Maisch, A., Späth, J. A., & Schröder, W. (2014). Bäumler, Singlet oxygen generation in porphyrin-doped polymeric surface coating enables antimicrobial effects on Staphylococcus aureus. Physical Chemistry Chemical Physics: PCCP, 16, 20598–20607.

    Article  PubMed  Google Scholar 

  61. Rowley, J. G., Farnum, B. H., Ardo, S., & Meyer, G. J. (2010). Iodide chemistry in dye-sensitized solar cells: making and breaking I−I bonds for solar energy conversion. Journal of Physical Chemistry Letters, 1, 3132–3140.

    Article  CAS  Google Scholar 

  62. Mosinger, J., Janošková, M., Lang, K., & Kubát, P. (2006). Light-induced aggregation of cationic porphyrins. Journal of Photochemistry and Photobiology A Chemistry, 181, 283–289.

    Article  CAS  Google Scholar 

  63. Vecchio, D., Gupta, A., Huang, L., Landi, G., Avci, P., Rodas, A., & Hamblin, M. R. (2015). Bacterial photodynamic inactivation mediated by methylene blue and red light is enhanced by synergistic effect of potassium iodide. Antimicrobial Agents and Chemotherapy, 59, 5203–5212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gardner, J. M., Abrahamsson, M., Farnum, B. H., & Meyer, G. J. (2009). Visible light generation of iodine atoms and I−I bonds: sensitized I− oxidation and I3− photodissociation. Journal of the American Chemical Society, 131, 16206–16214.

    Article  CAS  PubMed  Google Scholar 

  65. Boschloo, G., & Hagfeldt, A. (2009). Characteristics of the iodide/triiodide redox mediator in dye-sensitized solar cells. Accounts of Chemical Research, 42, 1819–1826.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by CONICET (PIP-2015 1122015 0100197 CO), UNRC-SECYT (PPI-2020 Res. 083/20) and ANPCYT (PICT 0667/16). J.E.D., M.G.A. and E.N.D. are Scientific Members of CONICET. M.L.A. thanks CONICET for the research fellowship.

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  1. IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas Y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36 Km 601, X5804BYA, Río Cuarto, Córdoba, Argentina

    Maximiliano L. Agazzi, Ezequiel D. Quiroga, M. Gabriela Alvarez & Edgardo N. Durantini

  2. IITEMA-CONICET Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas Y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36 Km 601, X5804BYA, Río Cuarto, Córdoba, Argentina

    Javier E. Durantini

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  1. Maximiliano L. Agazzi
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Agazzi, M.L., Durantini, J.E., Quiroga, E.D. et al. A novel tricationic fullerene C60 as broad-spectrum antimicrobial photosensitizer: mechanisms of action and potentiation with potassium iodide. Photochem Photobiol Sci 20, 327–341 (2021). https://doi.org/10.1007/s43630-021-00021-1

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