Engineering a motile biohybrid microrobot

脂质体是一种具有巨大潜力的靶向治疗药物的生物微粒。能够主动将自身推向病变部位的运动脂质体很难设计。已知一些细菌会主动向肿瘤迁移、靶向、主动穿透和定植肿瘤。我们的建议是，与其从头开始设计运动脂质体，不如搭上运动细菌的便车，将它们运送到离散的位置，让脂质体到达无法到达的目标。除了递送之外，工程细菌还将形成治疗本身的一部分，导致肿瘤细胞外基质的降解，我们将基于膜工程（Elani）设计脂质体，以控制对外部刺激的反应，并使用合成结构设计脂质体，使脂质体也能作为杀灭开关，以确保治疗后的细菌破坏（Ceroni andPolizzi）.我们还将有一个非遗传的外部杀死开关模块来控制安全性，通过利用过去三年开发的一套刺激响应脂质体（光，热，超声波，pH）来实现。

Liposomes are bioinspired particles which have tremendous potential fortargeted delivery of therapeutics. Motile liposomes that can actively propel themselves towards adiseased site are difficult to design. Some bacteria are known to actively migrate towards, target,actively penetrate and colonise tumours.Our proposition is that instead of designing motile liposomes from scratch, they can insteadhitchhike on motile bacteria to ferry them to discrete locations, allowing liposomes to reachotherwise inaccessible targets. In addition to delivery, the engineered bacteria will also form partof the therapy itself leading to degradation of the tumour extracellular matrix, allowing theliposomes to reach solid tumours.We will engineer the liposomes for controlled response to external stimuli based on membraneengineering (Elani) and engineer the liposomes with synthetic constructs enabling the liposomesto also act as a kill switch to ensure bacteria destruction after therapeutic delivery (Ceroni andPolizzi). We will also have a non-genetic external kill switch module to control safety, achieved byexploiting a suite of stimuli responsive liposomes have been developed over the past three years(light, heat, ultrasound, pH).