Near‐Infrared Organic Small‐Molecule Photosensitizer With O2 Self‐Supply for Cancer Photodynamic‐Photothermal Synergistic Therapy

Tumor hypoxia and heat resistance as well as the light penetration deficiency severely compromise the phototherapeutic efficacy, developing phototherapeutic agents to overcome these issues has been sought-after goal. Herein, a diradical-featured organic small-molecule semiconductor, namely TTD-CN, has been designed to show low exciton binding energy of 42 meV by unique dimeric π-π aggregation, promoting near-infrared (NIR) absorption beyond 808 nm and effective photo-induced charge separation. More interestingly, its redox potentials are tactfully manipulated for water splitting to produce O₂ and reduction of O₂ to generate O₂ ^•-. Besides, both ultrafast internal conversion and high-frequency stretching vibrational relaxation of C≡N bonds favor photothermy. Accordingly, TTD-CN nanoparticles have been prepared to exhibit spatiotemporally-synchronous O₂ and O₂ ^•- generation and 63.2% photothermal conversion under 808 nm laser irradiation for high-efficient photodynamic and photothermal synergistic therapy. These findings successfully realize NIR light-triggered spatiotemporally-synchronous O₂ self-supply, type-I photosensitization and superior photothermy in an organic small-molecule phototherapeutic agent, significantly boosting the development of phototherapy.