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

The precise regulation of structural and photophysical properties of β-anthracene-fused porphyrins is achieved via controlling the meso-substituents and core-metalation. The combining “β-meso-core” modification of porphyrin affords biocompatible PTA with intense NIR absorption and high PCE, enabling efficient PAI and excellent PTT performance in vitro and in vivo under 808 nm laser irradiation at biosafe intensities.

Abstract

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.