Engineering a motile biohybrid microrobot

脂质体是一种生物激发的颗粒，具有极大的靶向传递治疗药物的潜力。能够主动将自己推向死亡部位的可移动脂质体很难设计。众所周知，一些细菌会主动向肿瘤迁移、靶向、主动渗透和定居。我们的建议是，它们可以搭乘移动细菌的便车，将它们运送到离散的位置，从而使脂质体能够与其他无法触及的目标发生反应，而不是从头开始设计可移动的脂质体。除了递送，工程菌还将成为治疗本身的一部分，导致肿瘤细胞外基质的降解，使脂质体能够到达实体肿瘤。我们将基于膜工程(ELAI)设计脂质体，以控制对外部刺激的反应(ELAI)，并利用合成结构设计脂质体，使脂质体也能够在治疗输送后起到杀死开关的作用，以确保治疗输送后细菌的消灭(Ceroni和Polizzi)。我们还将拥有一个非遗传的外部杀死开关模块来控制安全性，这是通过利用过去三年开发的一套刺激响应型脂质体(光、热、超声波、pH)实现的。

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).