Seeing is believing: Efficiency evaluation of multifunctional ionic-dependent AIEgens for tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant public health threat with high rates of infection and mortality. Rapid and reliable theranostics of TB are essential to control transmission and shorten treatment duration. In this study, we report two cationic aggregation-inducing emission luminogens (AIEgens) named TTVP and TTPy, which have different functional charged moieties, to investigate their potential for simultaneous tracing and photodynamic therapy in TB infection. TTVP and TTPy exhibit intrinsic positive charges, excellent water solubility, and near-infrared (NIR) emission. Based on ionic-function relationships, TTVP, with more positive charges, demonstrates a stronger binding affinity to Mycobacterium marinum (M.m), (a close genetic relative of Mtb), compared to TTPy. Both TTVP and TTPy exhibit high efficiency in generating reactive oxygen species (ROS) when exposed to white light irradiation, enabling effective photodynamic killing of M.m in vitro. Additionally, we achieved long-term, real-time, noninvasive, continuous tracing, and evaluated therapeutic performance in vivo. Notably, TTVP outperformed TTPy in intracellular killing of M.m, suggesting a possible correlation between the labeling and photodynamic killing abilities of AIEgens. These findings provide valuable insights and a design basis for cationic AIEgens in TB research, offering potential advancements in TB theranostics.