Mitochondria-Damaging Self-Reporting Probe for Cancer Therapy

Mitochondrial damage induced by chemotherapeutic agents through disruption of the mitochondrial membrane potential (ΔΨ_m) remains a central challenge in drug development and evaluation. However, the assessment of ΔΨ_m-targeting drugs using commercially available fluorescent probes is often unreliable, as these dyes can interfere with, mask, or artificially amplify drug-induced mitochondrial dysfunction, frequently resulting in misleading conclusions and translational failure. Herein, we report a class of cationic chemotherapeutic small molecules (DPPs) possessing intrinsic fluorescence migration-based self-reporting capability, which enables direct and non-invasive monitoring of drug action without the need for external probes. Among them, DPP-1 and DPP-2 disrupt mitochondrial function, trigger excessive reactive oxygen species generation, and induce highly selective apoptosis. Remarkably, both compounds exhibit concentration-dependent mitochondrial-to-nuclear translocation, enabling the real-time visualization of therapeutic progression at the subcellular level. In vivo studies further confirm their potent tumor growth inhibition and negligible systemic toxicity effects. This self-reporting mitochondria-targeted chemotherapeutic platform provides a highly promising strategy for integrated cancer diagnosis and precision therapy.