Photo‐Triggered Fluorescence Polyelectrolyte Nanoassemblies: Manipulate and Boost Singlet Oxygen in Photodynamic Therapy

Abstract 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 1 O 2 generation in three stages: pre‐PDT (quenching 1 O 2 generation), during PDT (activating 1 O 2 generation), and post‐PDT (silencing 1 O 2 generation). This de novo strategy has for the first time realized remotely manipulating and boosting 1 O 2 generation in PDT, well resolving the critical and general challenges of limited photodynamic efficiency and side effects from nonspecific phototoxicity.