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Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes

Giuntini, F, Foglietta, F, Marucco, AM, Troia, A, Dezhkunov, NV, Pozzoli, A, Durando, G, Fenoglio, I, Serpe, L and Canaparo, R (2018) Insight into ultrasound-mediated reactive oxygen species generation by various metal-porphyrin complexes. Free Radial Biology and Medicine, 121. pp. 190-201. ISSN 0891-5849

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Abstract

Ultrasound is used to trigger the cytotoxicity of chemical compounds, known as sonosensitisers, in an approach called sonodynamic therapy (SDT), which is under investigation herein. The generation of reactive oxygen species (ROS) has been proposed as the main biological occurrence that leads to the cytotoxic effects, which are achieved via the synergistic action of two components: the energy-absorbing sonosensitiser and ultrasound (US), which are both harmless per se. Despite some promising results, a lack of investigation into the mechanisms behind US sonosensitiser-mediated ROS generation has prevented SDT from reaching its full potential.

The aim of this work is to investigate the US-responsiveness of a variety of metal-porphyrin complexes, free-base porphyrin and Fe(III), Zn(II) and Pd(II) porphyrin, by analyzing their ROS generation under US exposure and related bio-effects. All experiments were also carried out under light exposure and the results were used as references.

Our results show that porphyrin ultrasound-responsiveness depends on the metal ion present, with Zn(II) and Pd(II) porphyrin being the most efficient in generating singlet oxygen and hydroxyl radicals. ROS production efficiency is lower after ultrasound exposure than after light exposure, because of the various physico-chemical mechanisms involved in sensitiser activation. US and porphyrin-mediated ROS generation is oxygen-dependent and the activation of porphyrin by US appears to be more compatible with sonoluminescence-based photo-activation rather than a radical path process that occurs via the homolytic bond rupture of water. Notably, the cytotoxicity results reported herein, which are mirrored by ex-cellulo data, confirm that the type of ROS generation achieved by the US activation of intracellular porphyrins is pivotal to the effectiveness of cancer cell killing.

Item Type: Article
Uncontrolled Keywords: 0304 Medicinal And Biomolecular Chemistry, 0601 Biochemistry And Cell Biology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
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Date Deposited: 25 Jun 2018 09:26
Last Modified: 26 Oct 2018 20:11
DOI or Identification number: 10.1016/j.freeradbiomed.2018.05.002
URI: http://researchonline.ljmu.ac.uk/id/eprint/8884

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