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Updated: Jun 4, 2026
Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
Mitochondria-Damaging Self-Reporting Probe for Cancer Therapy
Hai Xu1, Yura Lee2, Sanghee Yoon3
1Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Republic of Korea.
Abstract:
Mitochondrial damage induced by chemotherapeutic agents through disruption of the mitochondrial membrane potential (ΔΨm) remains a central challenge in drug development and evaluation. However, the assessment of ΔΨm-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.
Insights
New self-reporting cancer drugs (DPPs) monitor their own mitochondrial action, avoiding unreliable probes. This allows precise tracking of drug effects for improved cancer therapy and diagnosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Chemotherapy often damages mitochondria, disrupting mitochondrial membrane potential (ΔΨm), a key factor in drug efficacy.
- Current methods using fluorescent probes to assess ΔΨm-targeting drugs are unreliable, leading to inaccurate conclusions and hindering drug development.
Purpose of the Study:
- To develop a novel class of self-reporting chemotherapeutic agents (DPPs) for direct, non-invasive monitoring of mitochondrial drug action.
- To evaluate the efficacy and safety of DPPs in preclinical cancer models.
Main Methods:
- Synthesized and characterized a series of cationic chemotherapeutic small molecules (DPPs) with intrinsic fluorescence.
- Assessed the ability of DPPs to disrupt mitochondrial function, induce reactive oxygen species (ROS), and trigger apoptosis.
- Investigated the mitochondrial-to-nuclear translocation of DPPs in real-time.
- Evaluated tumor growth inhibition and systemic toxicity in vivo.
Main Results:
- DPPs exhibit intrinsic fluorescence, enabling self-reporting of their action without external probes.
- DPP-1 and DPP-2 disrupt mitochondrial function, increase ROS generation, and induce selective apoptosis.
- Concentration-dependent mitochondrial-to-nuclear translocation of DPPs allows real-time visualization of therapeutic progression.
- In vivo studies demonstrated potent tumor growth inhibition with negligible systemic toxicity.
Conclusions:
- DPPs offer a reliable platform for monitoring mitochondria-targeted chemotherapy, overcoming limitations of current fluorescent probes.
- The self-reporting capability of DPPs facilitates real-time assessment of drug efficacy at the subcellular level.
- This mitochondria-targeted chemotherapeutic strategy holds promise for integrated cancer diagnosis and precision therapy.
