Sauvage Laboratory for Smart Materials, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.
Shenzhen Bay Laboratory, No. 9 Duxue Road, Shenzhen 518055, China.
ACS Nano. 2021 Jul 27;15(7):11543-11554. doi: 10.1021/acsnano.1c01573. Epub 2021 Jun 28.
Catalytically powered micro/nanobots (MNBs) can perform active movement by harnessing energy from chemical reactions and show tremendous potential in biomedical applications. However, the development of imageable MNBs that are driven by bioavailable fuels and possess multiple therapeutic functions remains challenging. To resolve such issues, we herein propose enzyme (urease) powered liquid metal (LM) nanobots that are naturally of multiple therapeutic functions and imaging signals. The main body of the nanobot is composed of a biocompatible LM nanoparticle encapsulated by polydopamine (PDA). Urease enzyme needed for the powering and desired drug molecules, .., cefixime trihydrate antibiotic, are grafted on external surfaces of the PDA shell. Such a chemical composition endows the nanobots with dual-mode ultrasonic (US) and photoacoustic (PA) imaging signals and favorable photothermal effect. These LM nanobots exhibit positive chemotaxis and therefore can be collectively guided along a concentration gradient of urea for targeted transportation. When exposed to NIR light, the LM nanobots would deform and complete the function change from active drug carriers to photothermal reagents, to achieve synergetic antibacterial treatment by both photothermal and chemotherapeutic effects. The US and PA properties of the LM nanoparticle can be used to not only track and monitor the active movement of the nanobots in a microfluidic vessel model but also visualize their dynamics in the bladder of a living mouse . To conclude, the LM nanobots demonstrated herein represent a proof-of-concept therapeutic nanosystem with multiple biomedical functionalities, providing a feasible tool for preclinical studies and clinical trials of MNB-based imaging-guided therapy.
催化动力微/纳米机器人（MNBs）可以通过利用化学反应中的能量进行主动运动，并在生物医学应用中展现出巨大的潜力。然而，开发由可生物利用的燃料驱动且具有多种治疗功能的可成像 MNB 仍然具有挑战性。为了解决这些问题，我们提出了由酶（脲酶）驱动的液态金属（LM）纳米机器人，其具有天然的多种治疗功能和成像信号。纳米机器人的主体由生物相容性的 LM 纳米颗粒封装在聚多巴胺（PDA）中组成。用于提供动力和所需药物分子的脲酶，...，头孢克肟三水合物抗生素，接枝在 PDA 壳的外表面。这种化学成分赋予纳米机器人双模超声（US）和光声（PA）成像信号和良好的光热效应。这些 LM 纳米机器人表现出正趋化性，因此可以沿着尿素浓度梯度进行集体导向，以进行靶向运输。当暴露于近红外光时，LM 纳米机器人会变形并完成从主动药物载体到光热试剂的功能变化，通过光热和化学治疗效果协同实现协同抗菌治疗。LM 纳米颗粒的 US 和 PA 特性不仅可用于跟踪和监测微流控容器模型中纳米机器人的主动运动，还可用于可视化它们在活体小鼠膀胱中的动力学。总之，本文展示的 LM 纳米机器人代表了具有多种生物医学功能的概念验证治疗性纳米系统，为基于 MNB 的成像引导治疗的临床前研究和临床试验提供了一种可行的工具。
