Near-infrared photosensitizers containing biscations for cellular membrane targeting fluorescence imaging and photodynamic therapy

Theranostic agents with near-infrared (NIR) absorbance, fluorescence emission, high ROS generation, efficient tumor-targeting, and prolonged retention are urgently needed. Developing cationic theranostic agents for photodynamic therapy and fluorescence imaging remains challenging. Agents with a single cationic group and bulky organic skeleton struggle with limited water solubility and poor tumor retention. To address this, three NIR biscationic organic photosensitizers, namely, TBVP, TTBVP, and TBTVP are designed by the combination of electron-donating, electron-withdrawing, and it-bridging units to achieve optimal energy levels. These photosensitizers displayed UV absorption from 450 to 600 nm and fluorescence emission from 600 to 800 nm. They disperse well in water and specifically target cell membranes due to strong electrostatic interactions with negatively charged phosphate groups in cellular membranes. These photosensitizers also generate high levels of ROS, making them promising PDT agents. Notably, TBTVP shows excellent tumor targeting, prolonged retention, and efficient metabolism both in vitro and in vivo, achieving 90 % tumor growth inhibition. This study highlights the significant potential of biscationic NIR agents as efficient phototheranostics for long-term cancer therapy.