Dual metabolic targeting liposomes potentiate triple-negative breast cancer radiosensitivity via glucose and glutathione starvation

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2025-11-01 Epub Date: 2025-10-19 DOI:10.1016/j.nano.2025.102870

Henan Zhang , Yanbin Liu , Xuezhi Gao , Guoli Ji , Yanzhen Zheng , Fei Luo , Xing Qi , Shasha Zhao , Shanghui Guan , Cong Wang , Ming Lu

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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) frequently develops resistance to radiotherapy, while its metabolic reliance on glucose and glutamine presents new therapeutic targets for radiotherapy sensitization. This study developed a targeted nanoliposome (G/B-Lip-R) co-delivering glucose oxidase (GOD) and buthionine sulfoximine (BSO) to enhance radiotherapy through dual metabolic intervention. GOD catalyzes glucose oxidation to generate hydrogen peroxide (H₂O₂) while depleting tumor energy supplies, whereas BSO inhibits glutathione (GSH) synthesis to disrupt redox homeostasis. Their synergistic action significantly elevates intracellular reactive oxygen species (ROS) levels, thereby potentiating radiosensitivity. Both in vitro and in vivo studies demonstrated that G/B-Lip-R effectively targets tumors and significantly improves radiotherapy outcomes. This work innovatively combines nanocarriers with dual metabolic pathway modulation, offering a novel strategy to overcome TNBC radioresistance with important clinical translation potential.

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双代谢靶向脂质体通过葡萄糖和谷胱甘肽饥饿增强三阴性乳腺癌放射敏感性。

三阴性乳腺癌（TNBC）经常对放疗产生耐药性，而其对葡萄糖和谷氨酰胺的代谢依赖为放疗增敏提供了新的治疗靶点。本研究开发了一种靶向纳米脂质体（G/ b - lipr）共同递送葡萄糖氧化酶（GOD）和丁硫氨酸亚砜胺（BSO），通过双代谢干预增强放疗。GOD催化葡萄糖氧化生成过氧化氢（H2O2），同时消耗肿瘤能量供应，而BSO抑制谷胱甘肽（GSH）合成，破坏氧化还原稳态。它们的协同作用显著提高细胞内活性氧（ROS）水平，从而增强放射敏感性。体外和体内研究均表明G/B-Lip-R能有效靶向肿瘤，显著改善放疗效果。本研究创新性地将纳米载体与双代谢途径调制相结合，为克服TNBC放射耐药提供了一种具有重要临床转化潜力的新策略。

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

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.