Yao Yongkang, Chen Shangjun, Yan Chenxu, Wang Junyou, Liu Jianjun, Zhu Wei-Hong, Fan Chunhai, Guo Zhiqian
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Angew Chem Int Ed Engl. 2025 Jan 10;64(2):e202416963. doi: 10.1002/anie.202416963. Epub 2024 Nov 14.
Photodynamic therapy (PDT) is a clinically approved therapeutic modality that has shown great potential for cancer treatment. However, there exist two major problems hindering PDT applications: the nonspecific phototoxicity requiring patients to stay in dark post-PDT, and the limited photodynamic efficiency. Herein, we report a photo-triggered porphyrin polyelectrolyte nanoassembling (photo-triggered PPN) strategy, in which porphyrin photosensitizer and photoswitchable energy accepter are assembled into polyelectrolyte micelles by a combined force of charge interaction and metal-ligand coordination. The polyelectrolyte-based PPN exhibits good biocompatibility, and bestows a unique "confining isolated" inner microenvironment for fully overcoming the π-π stacking of porphyrins with significant photodynamic efficiency (123-fold enhancement). Due to the high Förster resonance energy transfer (FRET) (91.5 %) between porphyrin and photoswitch in closed-form, we could use light as a specific trigger to modulate photoswitch between closed- and open-form, and manipulate the O generation in three stages: pre-PDT (quenching O generation), during PDT (activating O generation), and post-PDT (silencing O generation). This de novo strategy has for the first time realized remotely manipulating and boosting O generation in PDT, well resolving the critical and general challenges of limited photodynamic efficiency and side effects from nonspecific phototoxicity.
光动力疗法（PDT）是一种临床批准的治疗方式，已显示出在癌症治疗方面的巨大潜力。然而，存在两个主要问题阻碍了PDT的应用：非特异性光毒性要求患者在PDT后避光，以及光动力效率有限。在此，我们报告了一种光触发卟啉聚电解质纳米组装（光触发PPN）策略，其中卟啉光敏剂和光开关能量受体通过电荷相互作用和金属-配体配位的合力组装成聚电解质胶束。基于聚电解质的PPN具有良好的生物相容性，并赋予独特的“限制隔离”内部微环境，以充分克服卟啉的π-π堆积，具有显著的光动力效率（提高123倍）。由于在封闭形式下卟啉和光开关之间具有高福斯特共振能量转移（FRET）（91.5%），我们可以使用光作为特定触发来调节光开关在封闭和开放形式之间的转换，并在三个阶段操纵单线态氧的产生：PDT前（淬灭单线态氧的产生）、PDT期间（激活单线态氧的产生）和PDT后（使单线态氧的产生沉默）。这种全新的策略首次实现了在光动力疗法中远程操纵和增强单线态氧的产生，很好地解决了光动力效率有限和非特异性光毒性副作用这两个关键且普遍的挑战。
