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

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.

Retracted: Ultrasound‐triggered breast tumor sonodynamic therapy through hematoporphyrin monomethyl ether‐loaded liposome

“…Use of ultrasound with lower frequency and power improves the cavitation and concomitant biological effect (Hu et al, ; Qian, Zheng, & Chen, ). Multiple studies have shown that some sensitizers can be efficiently activated by ultrasound and generates cytotoxic ROS (Giuntini et al, ; Li et al, ; Rwei et al, ). Recently, a lot of sonosensitizers has been applied in SDT, including TiO 2 , chlorin, phthalocyanines and photofrin (Osaki et al, ; Rwei et al, ; Xu et al, ).…”

The bright side of sound: perspectives on the biomedical application of sonoluminescence

“…22 Recently some researchers have suggested US as a new tool to overcome certain drawbacks and improve the light delivery, mainly in the field of PDT and optogenetics. 5,[23][24][25][26][27] Light from sound…”

Analysis of sono-photodynamic effects with PpIX - >i<in Vitro>/i< and >i<in vivo>/i< studies

“…Sonoluminescence can be observed as occurring after stimulation in the ultrasonic frequency range, from 20 kHz up to 3 MHz, and is influenced by acoustic pressure, frequency, liquid proprieties, temperature and specific gas content. 19 The sonosensitizer activation is made feasible through the emission of sonoluminescent light over a broad range encompassing the Soret band of many porphyrin sonosensitizers as demonstrated by Umemura et al 15 . Sonoluminescence was recently observed by Giuntini et al 19 , studing the ultrasound-mediated various metal-porphyrin complexes activation.…”

“…19 The sonosensitizer activation is made feasible through the emission of sonoluminescent light over a broad range encompassing the Soret band of many porphyrin sonosensitizers as demonstrated by Umemura et al 15 . Sonoluminescence was recently observed by Giuntini et al 19 , studing the ultrasound-mediated various metal-porphyrin complexes activation. Alternatively, pyrolysis of sonosensitizers may be the source of ROS generation following SDT.…”

“…[14][15][16] The third one is high focal heat bringing about SS pirolysis and reactive oxygen species (ROS) formation, predominantly hydroxil radicals. [17][18][19] SDT was firstly raised by Umemura et al in 1990 noting that hematoporphyrin can be activated by ultrasound leading to significant antitumor effects. 15 An important challenge worldwide is to enable PDT application at deep-seated cancer.…”