Key Laboratory of Advanced Energy Materials Chemistry, (Ministry of Education), Renewable Energy Conversion and Storage Center (ReCAST), College of Chemistry, Nankai University, Tianjin, 300071, China.
Noyes Laboratory of Chemical Physics and the Beckman Institute, California Institute of Technology, Pasadena, CA, 91125, USA.
Angew Chem Int Ed Engl. 2019 Jun 11;58(24):8082-8086. doi: 10.1002/anie.201902815. Epub 2019 May 9.
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.
尽管光动力癌症疗法的一般机制已为人所知，但在分子水平上，光敏剂产生的单线态氧与基质分子之间的反应细节和后果仍难以捉摸。本文使用替莫泊芬作为光敏剂，结合场致液滴电离质谱和悬浮技术，研究了悬浮液滴气-水界面上单线态氧介导的 18:1 心磷脂和 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸-(1'-rac-甘油)(POPG)的“无壁”氧化反应。对于心磷脂和 POPG，每个不饱和油酰链都被氧化为丙烯基氢过氧化物，但令人惊讶的是，它不会进一步氧化。这归因于氧化链的亲水性增加，这促使它向水相移动，从而增加膜的通透性，并最终触发细胞死亡。
