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

IF 4.3 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Yao Liu, Zujun Que, Tianqi An, Zhipeng Zhang, Jianhui Tian
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引用次数: 0

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.

通过线粒体代谢抑制减轻肿瘤复发:一种新的近红外激光诱导治疗策略。
线粒体高代谢驱动的肿瘤复发仍然是癌症治疗中的一个关键挑战,因为异常的能量代谢会导致治疗抵抗和疾病进展。我们的目标是开发一种多功能纳米平台,结合线粒体代谢抑制、光热治疗和控制化疗来克服肿瘤复发机制。通过分子自组装,共负载阿霉素(DOX)和一氧化碳(CO)前药,设计了可生物降解的聚多巴胺纳米颗粒(PDA-DOX-CO NPs)。pd -DOX- co NPs表现出三种协同治疗作用:(1)光热消融(48.38°C肿瘤热疗),(2)co介导的线粒体抑制,(3)时空控制DOX释放。在HCT-116肿瘤模型中,近红外照射下的PDA-DOX-CO NPs诱导60%的肿瘤完全消融。组织病理学分析证实了治疗后肿瘤显著的细胞凋亡诱导和线粒体形态改变。这种“代谢阻断+能量消耗+精确递送”的模式为肿瘤复发提供了协同解决方案,通过线粒体靶向的多模式作用显示出增强的治疗效果和生物安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biological Procedures Online
Biological Procedures Online 生物-生化研究方法
CiteScore
10.50
自引率
0.00%
发文量
16
审稿时长
>12 weeks
期刊介绍: iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.
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