Efficient Near-Infrared Photosensitizer with Aggregation-Induced Emission for Imaging-Guided Photodynamic Therapy in Multiple Xenograft Tumor Models

Photodynamic therapy (PDT) strategy has been widely used in tumor treatment, and the reagents for reactive oxygen species (ROS) play a crucial role. Herein, we develop a fluorogen (TTB) containing an electron-accepting benzo[1,2-<i>b</i>:4,5-<i>b</i>']dithiophene 1,1,5,5-tetraoxide core and electron-donating 4,4'-(2,2-diphenylethene-1,1-diyl)bis(<i>N</i>,<i>N</i>-diphenylaniline) groups for image-guided targeting PDT application. TTB exhibits a prominent aggregation-induced emission (AIE) property with strong near-infrared (NIR) fluorescence in aggregates and is capable of efficiently generating ROS of O₂^•- and ¹O₂ under white light irradiation. The nanoparticles (RGD-4R-MPD/TTB NPs) with NIR emission (∼730 nm), high photostability, and low dark cytotoxicity are fabricated by encapsulating TTB within polymeric matrix and then modified with RGD-4R peptide. They show excellent performance in targeting PDT treatment of PC3, HeLa, and SKOV-3 cancer cells <i>in vitro</i>. The investigations on pharmacokinetics, biodistribution, and long-term tracing <i>in vivo</i> reveal that RGD-4R-MPD/TTB NPs can selectively accumulate in tumors for real-time, long-term image-guided PDT treatment. The RGD-4R-MPD/TTB NPs-mediated PDT in multiple xenograft tumor models disclose that the growth of cervical, prostate, and ovarian cancers in mice can be effectively inhibited. These results demonstrate that the reagents employing NIR fluorogen TTB as a photosensitizer could be promising candidates for <i>in vivo</i> image-guided PDT treatments of tumors.