A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between NO and PDT, the NO acts as the loaded gunpowder inside a ‘grenade’, ‘explosively’ amplifying the therapeutic effects that the light responsive ‘fuse’ Ce6 could exert. The present work may well serve as an inspiration for future creative approaches of photodynamic cancer therapy.

谷胱甘肽（GSH）敏感的超分子一氧化氮（NO）纳米发生器被开发为用于增强光动力疗法（PDT）的多面手。通过类似于乐高的宿主-客体相互作用，将GSH敏感的NO前药整合到系统中，纳米载体不仅可以消耗细胞内GSH，而且可以通过NO介导的血管舒张来缓解肿瘤部位的缺氧。此外，NO和活性氧物种（ROS）之间的反应可产生具有增强的杀生物活性的活性氮物种（RNS），该活性氧物种是由α-环糊精（α-CD）共轭的S-亚硝基硫醇和光活化的二氢卟酚e6（Ce6）产生的） 分别。由于NO和PDT之间的多种综合作用，NO充当了“手榴弹”内的负载火药，“爆炸性地”放大了对光敏感的“保险丝” Ce6可以发挥的治疗作用。当前的工作可能会为光动力癌症治疗的未来创新方法提供灵感。