Su Yonghui, Guo Dongqun, Liang Yinghao, Meiheriban Tuerdimaimaiti, Chen Siyu, Tang Qian, Chen Xiqian, Huang Yan, Zhong Jianqiao, Liu Zongjunlin
Department of Breast Surgery, School of Medicine, the First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361003, P. R. China.
Department of Urology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, P. R. China.
J Nanobiotechnology. 2025 Aug 11;23(1):557. doi: 10.1186/s12951-025-03636-z.
Cancer treatment commonly involves radiation as a primary therapy, affecting nearly two-thirds of patients. The use of combination therapies is gaining traction, with the aim of achieving synergistic effects through the pharmacological interactions of multiple treatments.
In this study, we present a Mn-Gd-based bimetallic nanoplatform resembling a virus, designed with a rough surface for anchoring glucose oxidase enzymes (GOx) and coating with extracellular vehicles (EVs) on the outer layer (VMn-Gd@GOx-EVs). This platform enables a synergistic approach by combining radiation therapy (RT) with oxidative therapy. The nanoplatform offers four key benefits: targeted delivery to tumors through EVs, Mn and Gd ion release triggered by the tumor microenvironment, GOx-induced generation of HO and acidic conditions for subsequent Fenton-like reactions, and relief from hypoxia to enhance RT.
Remarkably, the VMn-Gd@GOx-EVs platform effectively induces cell death in breast carcinoma models both in vitro and in vivo by harnessing the combined effects of RT and reactive oxygen species (ROS) generated by Mn ion catalysis under X-ray irradiation. Moreover, with its magnetic resonance imaging capabilities, this multi-functional diagnostic and therapeutic platform shows significant potential for clinical tumor treatment.
癌症治疗通常将放疗作为主要疗法，近三分之二的患者会接受放疗。联合疗法的应用越来越广泛，旨在通过多种治疗手段的药理相互作用实现协同效应。
在本研究中，我们展示了一种基于锰-钆的双金属纳米平台，其形似病毒，表面粗糙以锚定葡萄糖氧化酶（GOx），外层包覆细胞外囊泡（EVs）（VMn-Gd@GOx-EVs）。该平台通过将放射治疗（RT）与氧化疗法相结合，实现了一种协同方法。该纳米平台具有四个关键优势：通过EVs实现对肿瘤的靶向递送、肿瘤微环境触发锰和钆离子释放、GOx诱导产生羟基自由基（HO）以及酸性条件以进行后续类芬顿反应、缓解缺氧以增强放疗效果。
值得注意的是，VMn-Gd@GOx-EVs平台通过利用放疗与X射线照射下锰离子催化产生的活性氧（ROS）的联合效应，在体外和体内乳腺癌模型中均有效地诱导细胞死亡。此外，凭借其磁共振成像能力，这种多功能诊断和治疗平台在临床肿瘤治疗中显示出巨大潜力。
