Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13526-13530. doi: 10.1002/anie.202004180. Epub 2020 Jun 3.
Synthetic polymer vesicles spur novel strategies for producing intelligent nanodevices with precise and specific functions. Engineering vesicular nanodevices with tunable permeability by a general platform without involving trade-offs between structural integrity, flexibility, and functionality remains challenging. Herein, we present a general strategy to construct responsive nanoreactors based on polyion complex vesicles by integrating stimuli-responsive linkers into a crosslinking membrane network. The formulated ROS-responsive nanoreactor with self-boosting catalytic glucose oxidation could protect glucose oxidase (GOD) to achieve cytocidal function by oxidative stress induction and glucose starvation, which is ascribed to stimuli-responsive vesicle expansion without fracture and size-selective cargo release behavior. The GOD-loaded therapeutic nanoreactor induced an immunostimulatory form of cell death by pyroptosis, which has the great potential to prime anti-tumor immune responses.
合成聚合物囊泡激发了生产具有精确和特定功能的智能纳米器件的新策略。通过一个通用平台，在不牺牲结构完整性、灵活性和功能性的前提下，对具有可调渗透性的囊泡纳米器件进行工程设计仍然具有挑战性。在此，我们提出了一种通过将响应性连接子整合到交联膜网络中，基于聚离子复合物囊泡构建响应性纳米反应器的通用策略。所构建的具有 ROS 响应性的纳米反应器通过自增强催化葡萄糖氧化，可以保护葡萄糖氧化酶（GOD），通过氧化应激诱导和葡萄糖饥饿实现细胞毒性功能，这归因于响应性囊泡的扩张而不破裂和具有尺寸选择性的货物释放行为。负载 GOD 的治疗性纳米反应器通过细胞焦亡诱导一种免疫刺激性的细胞死亡形式，这具有引发抗肿瘤免疫反应的巨大潜力。
