Extended π-Conjugative Carbon Nitride for Single 1064 nm Laser-Activated Photodynamic/Photothermal Synergistic Therapy and Photoacoustic Imaging.

The synergetic photodynamic/photothermal therapy, activated via a single-second near-infrared (NIR-II) laser and guided by photoacoustic imaging (PAI), receives significant attention for precise in vivo therapy. However, due to the lack of a corresponding theranostic agent, it faces a great challenge for practical clinical implementation. Here, we present a single diagnostic and therapeutic nanoplatform named carbon nitride nanoparticles (CN-NPs) for efficient NIR-II PAI-guided photodynamic therapy (PDT)/photothermal therapy (PTT). The CN-NPs were obtained by incorporating an aromatic compound (PTCDA) with a large π-structure into melem by high-temperature polymerization. The absorption of the obtained CN-NPs was significantly enhanced compared with pristine melem. Under 1064 nm laser illumination, sufficient reactive oxygen species (ROS) generated by CN-NPs could reduce the mitochondrial membrane potential. Moreover, the CN-NPs exhibited an efficient PTT effect through improved photothermal stability and high photo-to-heat conversion efficiency (47.6%). We were also able to monitor the accumulation and metabolism of CN-NPs in vivo of mice in real time using PAI. The in vivo experiments proved that the CN-NPs could inhibit tumor growth and recurrence completely under 1064 nm. Thus, the proposed innovative strategy would open a new avenue to explore and construct NIR-II responsive nanoplatforms with enhanced performance and safety for multimodal phototheranostics.