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Published on: February 9, 2021
Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic
Yao Liu1, Zujun Que1, Tianqi An1
1Clinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, No. 274 Zhijiang Middle Road, Shanghai, 200071, China.
Abstract:
Tumor recurrence driven by mitochondrial hypermetabolism remains a critical challenge in cancer therapy, as aberrant energy metabolism fuels therapeutic resistance and disease progression. We aimed to develop a multifunctional nanoplatform combining mitochondrial metabolism inhibition, photothermal therapy, and controlled chemotherapy to overcome tumor recurrence mechanisms. Biodegradable polydopamine nanoparticles (PDA-DOX-CO NPs) were engineered via molecular self-assembly, co-loading doxorubicin (DOX) and a carbon monoxide (CO) prodrug. The PDA-DOX-CO NPs demonstrated three synergistic therapeutic effects: (1) Photothermal ablation (48.38 °C tumor hyperthermia), (2) CO-mediated mitochondrial suppression, and (3) Spatiotemporally controlled DOX release. In HCT-116 tumor models, PDA-DOX-CO NPs with NIR irradiation induced 60% tumor complete ablation. Histopathological analysis confirmed significant apoptosis induction and mitochondrial morphology alterations in treated tumors. This "metabolic blockade + energy depletion + precision delivery" paradigm provides a synergistic solution to tumor recurrence, demonstrating enhanced therapeutic efficacy and biosafety through mitochondrial-targeted multimodal action.
Insights
This study presents a novel nanoplatform to combat tumor recurrence by inhibiting mitochondrial metabolism, using photothermal therapy, and delivering chemotherapy. This approach effectively suppresses tumor growth and enhances therapeutic outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Tumor recurrence is a major challenge in cancer therapy, often driven by mitochondrial hypermetabolism.
- Aberrant cancer cell energy metabolism contributes to therapeutic resistance and disease progression.
Purpose of the Study:
- To develop a multifunctional nanoplatform for cancer therapy.
- To combine mitochondrial metabolism inhibition, photothermal therapy, and chemotherapy to overcome tumor recurrence.
Main Methods:
- Engineered biodegradable polydopamine nanoparticles (PDA-DOX-CO NPs) via molecular self-assembly.
- Co-loaded nanoparticles with doxorubicin (DOX) and a carbon monoxide (CO) prodrug.
- Investigated synergistic therapeutic effects including photothermal ablation, CO-mediated mitochondrial suppression, and controlled DOX release.
Main Results:
- PDA-DOX-CO NPs achieved 48.38 °C tumor hyperthermia upon near-infrared (NIR) irradiation.
- Demonstrated synergistic effects: photothermal ablation, mitochondrial suppression via CO, and precise DOX delivery.
- Achieved 60% tumor complete ablation in HCT-116 tumor models.
- Histopathology confirmed significant apoptosis and altered mitochondrial morphology.
Conclusions:
- The developed nanoplatform offers a synergistic "metabolic blockade + energy depletion + precision delivery" strategy.
- This multimodal approach effectively targets tumor recurrence mechanisms.
- Demonstrated enhanced therapeutic efficacy and biosafety through mitochondrial-targeted action.
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