Super-resolution imaging with a mitochondria-targeted fluorescent probe: Evaluation of chemotherapy-induced hepatorenal injury.

With the rising global incidence of cancer, anticancer drugs including cisplatin (DDP) and sunitinib (SU) are being widely used in clinical practice. However, severe nephrotoxicity of DDP and prominent hepatotoxicity of SU drastically restrict their clinical application. Therefore, real-time monitoring of liver and kidney function, along with early intervention of tissue damage progression, is essential during treatment. To address this challenge, we have herein developed a mitochondria-targeted super-resolution fluorescent probe ARP for hypochlorous acid (HClO). ARP's dual recognition sites and dual-signal detection ability significantly enhance its detection accuracy. Combined with super-resolution imaging technology, ARP elucidates the mechanism of ROS transformation induced by DDP and SU at the subcellular level. In vivo assays further validate the tissue-damage mechanisms of these two drugs and evaluate the protective effect of N-acetylcysteine (NAC) on the kidney and of silybin on the liver against drug-induced injury. The results demonstrate that both protective agents effectively alleviate hepatokidney damage without compromising the anti-tumor efficacy of the chemotherapeutic drugs. Hence, this work elucidates the anti-tumor and tissue injury mechanisms of DDP and SU in complex biological systems, providing a new strategy for mitigating drug-induced organ toxicity and offering a solid experimental basis for the rational design of clinical tumor chemotherapy regimens.