Phototheranostic Zinc Porphyrin Nanoparticles Triggered by an 808 nm Laser: NIR-II Fluorescence/Photoacoustic Imaging-Guided Combined Photothermal/Photodynamic/NO Therapy

Single-wavelength lasers that trigger intelligently designed multifunctional theranostic nanoplatforms are urgently needed for early cancer diagnosis and imaging-guided therapy. In this study, a novel zinc porphyrin, Por-TR, was fabricated by incorporating thiophene as a donor and introducing electron acceptors on both sides to expand the conjugation. The presence of multiple flexible chains in the molecular structure of Por-TR inhibits π-π stacking, which allows it to form J nanoaggregates when coassembled with DSPE-PEG2000, demonstrating maximum absorption at approximately 808 nm. These Por-TR NPs provide NIR-II fluorescence/PA dual-modal signals for imaging and serve as a combined PTT/PDT therapeutic agent, making them a suitable multifunctional theranostic nanoplatform. To further improve their therapeutic effects, we embedded a thermosensitive NO donor, BNN6, in the Por-TR nanosystem to achieve combined PDT/PTT/NO therapy. Intravenous injection of Por-TR-NO NPs into 4T1 tumor-bearing mice enabled the accurate observation of tumor location via NIR-II fluorescence/PA dual-modal imaging. In vivo therapy results show that the Por-TR-NO NPs exhibited remarkable antitumor efficacy in combined PTT/PDT/NO therapy, which was triggered by an 808 nm laser. Overall, this nanoplatform offers a versatile approach to cancer diagnosis and treatment.