Precisely Tailored Annulated Porphyrin with Intense NIR Absorption for Highly Efficient Photothermal Therapy and Photoacoustic Imaging.

Constructing near-infrared (NIR) phototherapy agents with good biosafety is highly desirable for cancer therapy. Herein, the combined "β-meso-core" engineering of porphyrin produces excellent photothermal/photoacoustic agents that exhibit locally excited NIR bands with high molar extinction coefficients reaching 105 scale. The β-anthracene fusion of porphyrins via retro-Diels-Alder reactions extends the π-systems, generating red-shifted and intensified Q bands with narrow half-widths. The change of meso-substituents leads to distorted, non-aggregated molecules with improved solubility and fine-tunes the photophysical characteristics. The core coordination of copper ions promotes non-radioactive decay in the energy-releasing process and enhances photobleaching resistance. The biocompatible nanoparticles encapsulating the designed porphyrin exhibit a high photothermal conversion efficiency of 68% and promising photoacoustic responses, enabling effective photoacoustic imaging-guided photothermal therapy in vivo at a safe laser intensity (808 nm, 0.3 W cm- 2). This study provides a novel strategy in the molecular engineering of porphyrin for designing highly efficient photothermal agents.