A novel drug-loaded pathogen-mimicking nanocomplex has been constructed for synergistic chemo-immunotherapy using detoxified lipopolysaccharide coated mesoporous silica nanoparticle. Detoxified lipopolysaccharide behaves as a dual-purpose entity that not only effectively mimics the function of the natural pathogen for triggering immune responses but also acts as a lid for inhibiting premature chemical drug release. In this approach, a knock-on effect would be observed at site of tumor: firstly, pathogen-mimicries elicited the elevated production of ROS; secondly, excessive production of ROS in turn oxidized the arylboronic ester to realize controlled chemotherapy; thirdly, in addition to inducing ROS generation, the nanocomplex would self-stimulate macrophages activation which subsequently activated cytotoxic T cells. Importantly, chemotherapy and immunotherapy were acting in a synergistic manner to inhibit solid tumor growth. Moreover, chemotherapeutic agents could be effectively released upon exposure to self-stimulating oxidative stress in which external addition of ROS was avoided. This proof of concept might open the door to a new generation of carrier materials in the field of cancer therapy.

中文翻译：

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病原体模拟纳米复合物：用于化学免疫治疗的肿瘤微环境中的自刺激氧化应激

使用解毒脂多糖包被的介孔二氧化硅纳米颗粒构建了一种新型的载药病原体模拟纳米复合物，用于协同化学免疫治疗。解毒脂多糖具有双重作用，不仅可以有效模拟天然病原体触发免疫反应的功能，还可以作为抑制化学药物过早释放的盖子。在这种方法中，将在肿瘤部位观察到连锁效应：首先，病原体模拟引起 ROS 的产生增加；其次，过量产生的ROS反过来氧化芳基硼酸酯以实现可控化疗；第三，除了诱导 ROS 生成外，纳米复合物还会自我刺激巨噬细胞激活，随后激活细胞毒性 T 细胞。重要的，化学疗法和免疫疗法以协同方式抑制实体瘤的生长。此外，化学治疗剂可以在暴露于自刺激氧化应激时有效释放，其中避免了外部添加 ROS。这一概念验证可能为癌症治疗领域的新一代载体材料打开大门。