Selective amplification of reactive oxygen species (ROS) generation in tumor cells has been recognized as an effective strategy for cancer therapy. However, an abnormal tumor metabolism, especially the mitochondrial glutaminolysis, could promote tumor cells to generate high levels of antioxidants (e.g., glutathione) to evade ROS-induced damage. Here, we developed a tumor-targeted nanoparticle (NP) platform for effective breast cancer therapy via combining inhibition of mitochondrial glutaminolysis and chemodynamic therapy (CDT). This NP platform is composed of bovine serum albumin (BSA), ferrocene, and purpurin. After surface decoration with a tumor-targeting aptamer and then intravenous administration, this NP platform could target tumor cells and release ferrocene to catalyze hydrogen peroxide (H₂O₂) into the hydroxyl radical (·OH) for CDT. More importantly, purpurin could inhibit mitochondrial glutaminolysis to concurrently prevent the nutrient supply for tumor cells and disrupt intracellular redox homeostasis for enhanced CDT, ultimately leading to the combinational inhibition of tumor growth.

中文翻译：

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纳米颗粒介导的线粒体谷氨酰胺分解抑制放大氧化应激用于联合癌症治疗

肿瘤细胞中活性氧（ROS）生成的选择性放大已被认为是癌症治疗的有效策略。然而，异常的肿瘤代谢，尤其是线粒体谷氨酰胺分解，可以促进肿瘤细胞产生高水平的抗氧化剂（如谷胱甘肽）来逃避 ROS 诱导的损伤。在这里，我们开发了一个肿瘤靶向纳米颗粒 (NP) 平台，通过结合抑制线粒体谷氨酰胺分解和化学动力学疗法 (CDT) 来有效治疗乳腺癌。该 NP 平台由牛血清白蛋白 (BSA)、二茂铁和红紫组成。用靶向肿瘤的适体进行表面修饰，然后静脉给药后，该NP平台可以靶向肿瘤细胞并释放二茂铁催化过氧化氢（H ₂ O₂ ) 转化为羟基自由基(·OH) 用于CDT。更重要的是，红紫素可以抑制线粒体谷氨酰胺分解，同时阻止肿瘤细胞的营养供应，并破坏细胞内氧化还原稳态以增强 CDT，最终导致肿瘤生长的联合抑制。