Biohybrid bacteria–based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque–driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.

中文翻译：

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用于增加肿瘤浸润的磁扭矩驱动活体微型机器人

基于生物混合细菌的微型机器人越来越被认为是用于靶向癌症治疗的有前途的外部可控载体。特别是磁场已被用作传递能量和引导其运动的安全手段。到目前为止，在这种情况下使用的磁控制策略依赖于可扩展性较差的磁场梯度，需要主动位置反馈，或者不适合在体内扩散分布。在这里，我们提出了一种磁扭矩驱动控制方案，用于增强通过生物屏障的转运，补充了一系列细菌表现出的向肿瘤核心的先天滑行，如图所示磁螺菌作为一种磁响应模式生物。这种混合控制策略易于扩展，独立于位置反馈，适用于由循环系统分散的细菌微型机器人。我们观察到磁响应细菌在血管内皮模型中的易位增加了四倍，并发现驱动增加运输的主要机制是细胞界面处的扭矩驱动表面探索。使用球体作为三维肿瘤模型，荧光标记的细菌在暴露于旋转磁场的样本中以高达 21 倍的高信号定植于其核心区域。除了增强传输之外，我们还证明了我们的控制方案提供了更多优势，包括基于感应检测的闭环优化的可能性，以及空间选择性驱动以减少脱靶效应。最后，在小鼠全身静脉注射后，我们发现细菌肿瘤积累显着增加，这支持了在临床上为磁响应生物混合微型机器人部署这种控制方案的可行性。