Enzyme-Powered Liquid Metal Nanobots Endowed with Multiple Biomedical Functions

Abstract

Catalytically powered micro/nanobots (MNBs) can perform active movement by harnessing energy from in situ 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, e.g., 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 in vivo. 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.

Micro‐Nano Motors with Taxis Behavior: Principles, Designs, and Biomedical Applications

“…Xu et al demonstrated a urease-powered Ga-In-Sn alloy-based Liquid metal (LM) MNMs as an active nanoplatform for therapeutic and potential diagnostic functions. [23] The urease-powered LM@ polydopamine (PDA) nanobots exhibit enhanced diffusion in uniform urea solution and positive chemotaxis behavior along the urea gradient. In addition, MNMs can undergo morphological transformation under the trigger of near-infrared (NIR) light, resulting in rice shape of high photothermal conversion efficiency, which can be used for photothermal antimicrobial therapy (Figure 2C).…”

“…C) Positive chemotaxis of LM@polydopamine (PDA) nanobots toward an agarose gel containing 50 mm urea. Reproduced with permission [23]. Copyright 2021, American Chemical Society.…”

Micro‐/Nanorobots in Antimicrobial Applications: Recent Progress, Challenges, and Opportunities

“…Reproduced with permission. [ 71 ] Copyright 2021, American Chemical Society. D) Rotifer based microrobots through the accumulation of functionalized microbeads.…”

“…demonstrated enzyme‐powered liquid metal‐based (LM) nanorobots for bacterial killing and dynamic contrast‐enhanced imaging (Figure 3C). [ 71 ] The modification of urease endows robots to perform drug transportation along the concentration gradient of urea. Meanwhile, the LM nanorobots can serve as contrast agents for ultrasound and photoacoustic imaging to track the active motion of nanorobots in artificial vascular models and the bladder of mice.…”

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

“…Recent research has tended to exploit the motion of synthetic swimmers near boundaries, where non-slip conditions minimize flow velocity, drag force is reduced, and upstream manipulation is easier. Catalytic approaches have been widely investigated (17)(18)(19)(20)(21)(22), and Katuri et al demonstrated a controlled crossstream motion of janus particles, which could mimic the motion of natural microswimmers and be exploited to reach vessel boundaries (23). Importantly, some approaches have already managed to manipulate microswimmers upstream when they are close to a wall.…”