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Dual-responsive biohybrid neutrobots for active target delivery
Science Robotics ( IF 26.1 ) Pub Date : 2021-03-24 , DOI: 10.1126/scirobotics.aaz9519
Hongyue Zhang 1 , Zesheng Li 1 , Changyong Gao 2 , Xinjian Fan 2 , Yuxin Pang 3 , Tianlong Li 2 , Zhiguang Wu 1 , Hui Xie 2 , Qiang He 1
Affiliation  

Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot (“neutrobot”) that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future.



中文翻译:

用于主动目标传递的双响应生物混合中性机器人

具有自我推进和导航能力的游泳生物混合微型机器人(例如,细菌或精子驱动的微型机器人)已成为一个令人兴奋的研究领域,这要归功于它们在身体难以到达的区域的可控运动,用于无创药物输送和治疗。然而,目前基于细胞的微型机器人在进入人体后很容易受到免疫攻击和清除。在这里,我们报告了一种基于中性粒细胞的微型机器人(“neutrobot”),它可以在体内主动向恶性胶质瘤输送货物。neutrobots 是通过天然中性粒细胞对大肠杆菌膜包裹的载药磁性纳米凝胶的吞噬作用构建的,其中大肠杆菌膜伪装提高了吞噬作用的效率,也防止了中性粒细胞内的药物泄漏。通过暴露在旋转磁场下的可控血管内运动,neutrobots 可以在大脑中自主聚集,随后通过 neutrobots 沿着炎症因子梯度的正向趋化运动穿过血脑屏障。与传统的药物注射相比,使用这种双响应neutrobots进行靶向药物递送大大抑制了肿瘤细胞的增殖。继承了目前人工微型机器人无法比拟的天然中性粒细胞的生物学特性和功能,本研究开发的中性粒细胞为未来的精准生物医学提供了一条有前景的途径。

更新日期:2021-03-25
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