Mass Spectrometric Study of Acoustically Levitated Droplet Illuminates Molecular-Level Mechanism of Photodynamic Therapy for Cancer involving Lipid Oxidation

Abstract

Even though the general mechanism of photodynamic cancer therapy is known, the details and consequences of the reactions between the photosensitizer‐generated singlet oxygen and substrate molecules remain elusive at the molecular level. Using temoporfin as the photosensitizer, here we combine field‐induced droplet ionization mass spectrometry and acoustic levitation techniques to study the "wall‐less" oxidation reactions of 18:1 cardiolipin and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐(1′‐rac‐glycerol) (POPG) mediated by singlet oxygen at the air–water interface of levitated water droplets. For both cardiolipin and POPG, every unsaturated oleyl chain is oxidized to an allyl hydroperoxide, which surprisingly is immune to further oxidation. This is attributed to the increased hydrophilicity of the oxidized chain, which attracts it toward the water phase, thereby increasing membrane permeability and eventually triggering cell death.

Additional Information

© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Manuscript received: March 5, 2019; Accepted manuscript online: April 23, 2019; Version of record online: May 9, 2019. This work was supported by the Beckman Institute at Caltech and by NSF grant CHE-1508825 (J.L.B.). This work is dedicated to the 100th anniversary of Nankai University. The authors declare no conflict of interest.

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