The hyperactive energy metabolism mostly contributes the tumor cells growth and proliferation. Herein, the intelligent nanoparticles (P-B-D NPs) obtained by loading BAY-876 and doxorubicin (Dox)-Duplex into nanoparticles composed of disulfide bond (SS) containing polymer are reported, which provide an efficient resistance of tumor cells energy metabolism and tumor growth to conquer malignant tumor. In response to the reducing microenvironment of tumor tissue, the SS bond can be disintegrated by intracellular glutathione to block the synthesis of lipid repair enzyme-glutathione peroxidase 4 for ferroptosis therapy. More importantly, the released BAY-876 can inhibit the functionality of glucose transporter 1, restricting the glucose uptake of tumor cells to a low energy metabolism status. Meanwhile, Dox-Duplex can interact with ATP to reduce intracellular ATP content and release Dox to kill tumor cells. Collectively, this work offers a new idea for restricting tumor cells energy metabolism to inhibit their proliferation.

中文翻译：

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能量转换抑制对肿瘤铁死亡治疗和化疗的可持续性

过度活跃的能量代谢主要有助于肿瘤细胞的生长和增殖。在本文中，通过加载BAY-876和多柔比星（DOX）-Duplex获得成二硫键（S组成的纳米颗粒中的纳米颗粒智能（PBD NPS） S）含聚合物被报告，其提供肿瘤细胞的能量代谢和肿瘤的有效电阻生长战胜恶性肿瘤。为响应肿瘤组织微环境的减少，S S键可被细胞内谷胱甘肽分解，阻断脂质修复酶-谷胱甘肽过氧化物酶4的合成，用于铁死亡治疗。更重要的是，释放的 BAY-876 可以抑制葡萄糖转运蛋白 1 的功能，将肿瘤细胞的葡萄糖摄取限制在低能量代谢状态。同时，Dox-Duplex 可与 ATP 相互作用，降低细胞内 ATP 含量，释放 Dox 杀死肿瘤细胞。总的来说，这项工作为限制肿瘤细胞能量代谢以抑制其增殖提供了新思路。