Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy

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, phot...

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Main Authors: Yao Liu, Zujun Que, Tianqi An, Zhipeng Zhang, Jianhui Tian
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Biological Procedures Online
Subjects:
Online Access:https://doi.org/10.1186/s12575-025-00283-4
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author Yao Liu
Zujun Que
Tianqi An
Zhipeng Zhang
Jianhui Tian
author_facet Yao Liu
Zujun Que
Tianqi An
Zhipeng Zhang
Jianhui Tian
author_sort Yao Liu
collection DOAJ
description 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.
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institution Kabale University
issn 1480-9222
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publishDate 2025-07-01
publisher BMC
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series Biological Procedures Online
spelling doaj-art-a0bc8cadbcc34772a129ecacdf69b6ae2025-08-20T04:01:24ZengBMCBiological Procedures Online1480-92222025-07-0127111610.1186/s12575-025-00283-4Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic StrategyYao Liu0Zujun Que1Tianqi An2Zhipeng Zhang3Jianhui Tian4Clinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineClinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s12575-025-00283-4Antitumor therapyCO gas therapyMitochondrial metabolismPhotothermal therapyChemotherapy
spellingShingle Yao Liu
Zujun Que
Tianqi An
Zhipeng Zhang
Jianhui Tian
Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
Biological Procedures Online
Antitumor therapy
CO gas therapy
Mitochondrial metabolism
Photothermal therapy
Chemotherapy
title Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
title_full Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
title_fullStr Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
title_full_unstemmed Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
title_short Mitigating Tumor Recurrence through Mitochondrial Metabolism Inhibition: A Novel NIR Laser-Induced Therapeutic Strategy
title_sort mitigating tumor recurrence through mitochondrial metabolism inhibition a novel nir laser induced therapeutic strategy
topic Antitumor therapy
CO gas therapy
Mitochondrial metabolism
Photothermal therapy
Chemotherapy
url https://doi.org/10.1186/s12575-025-00283-4
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