Cyclic Amplification of the Afterglow Luminescent Nanoreporter Enables the Prediction of Anti-cancer Efficiency.

Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Herein, we developed a novel cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated ROS. First, we promoted semiconducting polymer nanoparticles (PFODBT) as a novel candidate for emitting near-infrared afterglow luminescence. Second, the introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen ( 1 O 2 ). Third, 1 O 2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking ICD-associated immune responses through ROS-based oxidative stress. Notably, the afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O 2 generation and anti-cancer efficiency, respectively. Overall, our imaging strategy provided a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy, which may contribute to precise immunotherapy.