Physical Intelligence Department, Max Planck Institute for Intelligent Systems , Stuttgart 70569, Germany.
ACS Nano. 2017 Oct 24;11(10):9759-9769. doi: 10.1021/acsnano.7b02082. Epub 2017 Sep 6.
Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (e.g., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated Escherichia coli. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (i.e., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This in vitro model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in in vitro disease models (e.g., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body.
生物杂交细胞驱动的微系统为在微米尺度上实现软微型机器人提供了无与伦比的可能性。在这里,我们引入了一种由细菌驱动的微型游泳者,它将细菌的主动运动和传感能力与软双胶束微乳液的理想封装和粘弹性特性结合在一起,用于主动运输和输送货物(例如,成像剂、基因和药物)到活细胞。准单分散双乳液是用含有荧光成像剂的水芯合成的,作为本研究中的概念验证货物,而外部油壳则用链霉亲和素功能化,以实现生物素化的大肠杆菌的特异性和稳定附着。运动细菌有效地推动软微型游泳者穿过 Transwell 膜,将封装在胶束内的成像剂(即染料)主动递送到单层培养的 MCF7 乳腺癌和 J744A.1 巨噬细胞中,从而能够实时对活细胞进行细胞器(即线粒体、内质网和高尔基体)成像。该体外模型证明了所提出的软微型游泳者的概念验证可行性,并为在体外疾病模型(例如,器官芯片装置)和人体静止或低流速流体区域中主动和/或靶向运输和递送成像剂、药物、干细胞、siRNA 和治疗基因到活组织的潜在生物医学应用提供了希望。