Highly Photoreactive Semiconducting Polymers with Cascade Intramolecular Singlet Oxygen and Energy Transfer for Cancer-Specific Afterglow Theranostics

Afterglow luminescence provides ultrasensitive optical detection by minimizing tissue autofluorescence and increasing the signal-to-noise ratio. However, due to the lack of suitable unimolecular afterglow scaffolds, current afterglow agents are nanocomposites containing multiple components with limited afterglow performance and have rarely been applied for cancer theranostics. Herein, we report the synthesis of a series of oxathiine-containing donor-acceptor block semiconducting polymers (PDCDs) and the observation of their high photoreactivity and strong near-infrared (NIR) afterglow luminescence. We reveal that PDCDs absorb NIR light to undergo a photodynamic process to generate singlet oxygen (¹O₂), which intramolecularly transfers to and efficiently reacts with the oxathiine block to form the afterglow oxathiine intermediates due to the low Gibbs free energy changes required for this photoreaction. Following intramolecular afterglow energy transfer from the oxathiine donor block to the acceptor block, NIR afterglow emission is produced from PDCDs. Owing to the efficient cascade intramolecular photochemical process, PDCD-based nanoparticles achieve a higher brightness and longer NIR emission compared to most reported afterglow agents, even after ultrashort photoirradiation for only 3 s. Furthermore, the cascade photochemical process within PDCD can be inhibited after bioconjugation with a quencher-linked peptide. This allows the construction of a cancer-activatable afterglow theranostic probe (CATP) that only switches on the afterglow signal and photodynamic function in the presence of a cancer-overexpressed enzyme. Thereby, CATP represents the first afterglow phototheranostic probe that permits cancer-specific detection and photodynamic cancer therapy under preclinical settings. In summary, this study provides a molecular guideline to develop afterglow probes from photoreactive polymers.