Developing effective nanomedicines to cross the blood–brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T₁-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.

中文翻译：

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用于精确神经胶质瘤治疗诊断的超小氧化铁纳米颗粒的巨噬细胞膜伪装纳米簇

开发有效的纳米药物来跨越血脑屏障（BBB）以进行有效的神经胶质瘤治疗诊断仍然被认为是一项具有挑战性的任务。在这里，我们描述了超小型氧化铁纳米颗粒（USIO NP）的巨噬细胞膜（MM）包被的纳米簇（NC）的开发，该纳米簇具有双pH和活性氧（ROS）响应性，用于磁共振（MR）成像和化疗/原位神经胶质瘤的化学动力学治疗（CDT）。采用溶剂热法合成表面柠檬酸盐稳定的 USIO NP，依次用乙二胺和苯基硼酸进行改性，并与棉酚交联形成棉酚-USIO NC（G-USIO NC），并进一步用 MM 包覆。制备的平均尺寸为 99.9 nm 的 MM 包被的 G-USIO NC（G-USIO@MM NC）显示肿瘤微环境（TME）响应性棉酚和 Fe 释放，促进细胞内 ROS 产生和谷胱甘肽消耗。通过MM介导的BBB穿越和胶质瘤靶向，G-USIO@MM NCs可以通过棉酚介导的化疗和Fe介导的CDT特异性抑制体内原位胶质瘤。同时，USIO NPs可以在TME下与NCs分离，从而允许有效的T ₁加权神经胶质瘤MR成像。开发的 G-USIO@MM NC 具有简单的成分和作为交联剂的药物，有望用于神经胶质瘤治疗诊断，并可能扩展到治疗其他癌症类型。