Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
ACS Appl Mater Interfaces. 2020 Sep 16;12(37):41038-41046. doi: 10.1021/acsami.0c10372. Epub 2020 Sep 4.
Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of "smart" and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host-guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host-guest interaction and pH responsiveness of the water-soluble pillar[5]arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.
光动力疗法（PDT）已成为一种有前途且时空可控的癌症治疗方法。然而，在 PDT 过程中严重的皮肤光敏化限制了 PDT 的临床应用。因此，构建“智能”和多功能光敏剂引起了人们的极大兴趣。在此，我们通过主客体相互作用开发了一种靶向线粒体和 pH 开关的杂化超分子光敏剂。超分子光敏剂的 PDT 效果可以通过长循环过程中的Förster 共振能量转移（FRET）效应被猝灭，并在酸性肿瘤微环境中通过超分子光敏剂的解离被激活，这得益于主客体相互作用的动态特征和金纳米粒子上水溶性杯[5]芳烃的 pH 响应性。在杂化开关超分子光敏剂中合理整合靶向线粒体和还原型谷胱甘肽（GSH）消除功能，可延长 PDT 近线粒体生成的活性氧的寿命，并进一步放大 PDT 的效果。因此，开关超分子光敏剂的简便多功能构建不仅提供了靶向和精确的光疗，而且还提高了治疗效果，为 PDT 的临床应用提供了新途径。
