Dual-Functional Nanoplatform for Highly Controllable ROS Generation and Monitoring in ROS-Mediated Therapy

Reactive oxygen species (ROS) are being explored as a potential treatment, but accurate assessment of their efficacy is hindered by the dual roles of therapeutic intervention and diagnostic monitoring. Especially, ROS can alter lysosomal polarity by increasing membrane permeability. Therefore, ROS generation can be evaluated by monitoring the polarity changes of lysosomes. Hence, in this study, we developed a new lysosomal polarity-responsive carbon dot nanozyme (LF-CDs) that exerts peroxidase-like (POD-like) activity under light irradiation for controllable generation of ROS and sensing of ROS levels via lysosomal polarity response. Western blot analysis revealed that LF-CDs induced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation within cells through the generation of ROS, effectively regulating intracellular glucose metabolism. Importantly, the ROS produced by LF-CDs can cause lysosomal polarity variation and trigger a corresponding fluorescence change in LF-CDs, reflecting the generation of ROS and enabling in situ monitoring of the regulation of glucose metabolism by ROS. By combining photocatalytic property with fluorescence imaging, this work overcomes the limitations of traditional ROS monitoring, offering a new insight into the evaluation of the biological effects of ROS during therapeutic processes.