Cancer hallmarks allow the complexity and heterogeneity of tumor biology to be better understood, leading to the discovery of various promising targets for cancer therapy. An amorphous iron oxide nanoparticle (NP)‐based RNAi strategy is developed to co‐target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton‐like reaction. This strategy has the following features for systemic siRNA delivery: 1) siRNA encapsulation within NPs for improving systemic stability; 2) effective endosomal escape through osmotic pressure and/or endosomal membrane oxidation; 3) small size for enhancing tumor tissue penetration; and 4) triple functions (RNAi, Fenton‐like reaction, and MRI) for combinatorial therapy and in vivo tracking.

中文翻译：

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工程多功能RNAi纳米医学，以同时针对组合疗法的癌症标志。

癌症的标志使人们可以更好地理解肿瘤生物学的复杂性和异质性，从而导致发现了各种有希望的癌症治疗靶标。制定了基于非晶态氧化铁纳米粒子（NP）的RNAi策略，以共同靶向两个癌症标志。NP技术可通过沉默MCT4诱导肿瘤细胞酸中毒来调节糖酵解途径，并同时通过Fenton样反应加剧肿瘤细胞中的氧化应激。该策略具有全身siRNA传递的以下特征：1）siRNA封装在NP中，以提高系统稳定性。2）通过渗透压和/或内体膜氧化有效的内体逃逸；3）体积小，可增强肿瘤组织的穿透力；和4）三重功能（RNAi，类似于Fenton的反应，