Confined semiconducting polymers with boosted NIR light-triggered H₂O₂ production for hypoxia-tolerant persistent photodynamic therapy

Hypoxia featured in malignant tumors and the short lifespan of photo-induced reactive oxygen species (ROS) are two major issues that limit the efficiency of photodynamic therapy (PDT) in oncotherapy. Developing efficient type-I photosensitizers with long-term ˙OH generation ability provides a possible solution. Herein, a semiconducting polymer-based photosensitizer PCPDTBT was found to generate ¹O₂, ˙OH, and H₂O₂ through type-I/II PDT paths. After encapsulation within a mesoporous silica matrix, the NIR-II fluorescence and ROS generation are enhanced by 3-4 times compared with the traditional phase transfer method, which can be attributed to the excited-state lifetime being prolonged by one order of magnitude, resulting from restricted nonradiative decay channels, as confirmed by femtosecond spectroscopy. Notably, H₂O₂ production reaches 15.8 μM min⁻¹ under a 730 nm laser (80 mW cm⁻²). Further adsorption of Fe²⁺ ions on mesoporous silica not only improves the loading capacity of the chemotherapy drug doxorubicin but also triggers a Fenton reaction with photo-generated H₂O₂in situ to produce ˙OH continuously after the termination of laser irradiation. Thus, semiconducting polymer-based nanocomposites enables NIR-II fluorescence imaging guided persistent PDT under hypoxic conditions. This work provides a promising paradigm to fabricate persistent photodynamic therapy platforms for hypoxia-tolerant phototheranostics.