Nanozyme Microrobots: Programmable Spatiotemporal Catalysis for Targeted Therapy and Diagnostics

Abstract

Nanozyme microrobots combine catalytic nanomaterials with small-scale robotic control to deliver programmable, spatiotemporal catalysis for biomedical applications with precision. Actuated by external stimuli, such as magnetic, acoustic, optical, or chemical gradients, these systems localize and modulate catalytic activity on demand, overcoming long-standing limitations of bulk catalysis, including poor spatial precision, restricted substrate access, and limited adaptability in complex biological environments. By uniting targeted navigation with stimulus-responsive activation, nanozyme microrobots facilitate precise intervention in anatomically challenging and inaccessible niches, from biofilms to solid tumors, and support theranostic workflows with real-time readouts. This review focuses on design principles for integrating nanozymes with microrobotics, surveys actuation, automation, and control strategies, and highlights biomedical applications across biofilm infection control, oncology, and catalytic diagnostics. Together, the convergence of nanozyme catalysis and microrobotic mobility is yielding versatile, adaptive platforms with the potential to transform targeted diagnostics and therapy.

Keywords: biomedical robots; close‐loop feedback control; localized catalysis; reactive oxygen species; stimuli‐responsive actuation; structure‐activity relationships.

FIGURE 1

Microrobotics as a convergence platform for nanozyme functions. (Left) Nanozyme catalysis can be achieved with diverse materials, including metals, metal oxides, metal–organic frameworks (MOFs), and carbon‐based nanomaterials, together with their tunable catalytic mechanisms. (Right) Microrobotics provide multiple actuation methods (magnetic, electric, optical, ultrasound) and the concept of physical intelligence, encompassing mobility, reconfigurability, sensing, memory/logic, and targeting strategies. (Bottom) The convergence of these two domains yields nanozyme microrobots, where catalytic function is dynamically regulated by robotic motion and control. This integration enables mobility‐modulated and spatially resolved catalysis, supports integrated system design, and synergistic multifunctionality that facilitates translatable systems for practical applications, forming a unified platform for intelligent, controllable nanozyme‐based technologies.

FIGURE 2

Mobility‐modulated catalysis. (A) Assembly, control, and functional properties of robotic nanozyme assemblies. (B) Their mode of motion. (C) Catalytic activity in situ generated by motion dynamics. The 3,3′,5,5′‐tetramethylbenzidine (TMB) assay demonstrates the on‐site generation of ROS from H₂O₂ by the catalytically active (peroxidase‐like) nanozyme microrobots. Catalytic activity dynamics of (D) rolling, (E) vibrating, and (F) gliding motions. Adapted from Ref [25] under the Creative Commons CC‐BY‐NC‐ND license.

FIGURE 3

Spatially resolved catalysis. (A) Assembly, magnetic control, and functional properties of Fe₃O₄ nanoparticles‐based robotic superstructures. (B) Catalytic activity showing localized ROS generation around the superstructure, visualized by a 3,3′,5,5′‐tetramethylbenzidine (TMB) colorimetric assay. Adapted with Ref [31] under CC‐BY‐NC‐ND 4.0. (C) Schematic of the permanent magnet system used to generate a rotating magnetic field for targeted catalysis by Fe₃O₄ nanoparticle collectives. Sequential images (P1–P4) illustrate the movement of the nanoparticle collective over time and the progression of TMB catalysis from 0 to 10 min. Adapted with permission from Ref [80] (Copyright 2021, American Chemical Society). (D) Fabrication of nanozyme‐shelled microcapsules via a droplet‐templated microfluidic method. (E) Collective navigation of nanozyme‐shelled microcapsule assemblies within a bifurcated root canal model. (F) Targeted catalysis of nanozyme‐shelled microcapsules, showing localized catalytic activity restricted to one canal, as determined by the TMB assay. Adapted from Ref [26] under the Creative Commons CC‐BY‐NC‐ND license.

FIGURE 4

Integrated design of nanozyme robotics. (A) Formation of magnetic hydrogel micromachines (MHMs) capable of absorbing H₂O₂ solution and actively releasing the cargo when heated above the lower critical solution temperature (LCST). (B) Absorbance change of the TMB/H₂O₂ solution over time. Inset: snapshots of two experimental groups at 0, 3, and 5 min. (C) Comparison of active and passive release. The active group is heated via magnetothermal effect and actuated under a rotating magnetic field; the passive group reacts without heating or magnetic stimulation; the control group contains MHMs without H₂O₂ loading. Adapted from Ref [70] under the Creative Commons Attribution License. (D) Schematic illustration of ultrasound‐responsive catalytic microbubbles. (E) Peroxidase‐like catalytic activity of microbubbles before and after ultrasound treatment using the TMB assay. Pip‐Rh stands for piperacillin labeled with Rh. (F) Penetration depth of different samples within EPS‐mimicking gels. Adapted from Ref [71] under a Creative Commons Attribution NonCommercial License 4.0 (CC BY‐NC). (G) Schematic illustration of the ultrasound‐activated antibacterial mechanism and bone regeneration capability of the copper ferrite@MoS₂ heterojunction. Redox‐driven Fenton catalysis accelerates ROS generation, while microstreaming enhances transport for synergistic mechanical–chemical action; Cu²⁺ released from CFO@MoS₂ further promotes angiogenesis and osteogenesis. Adapted with permission from Ref [72] (Copyright 2025, Elsevier).

FIGURE 5

Biomedical applications of nanozyme robotics. (A) Precision programming and automation of the dabbing nanozyme microrobot, showing the superstructure extending and tapping the targeted surface. (B) Comparison of coating efficiency between dispersed Fe₃O₄ nanoparticles (IONP) treatment and IONP dabbing. Bright‐field microscopy (upper, scale bar: 500 µm) and confocal microscopy (lower, scale bar: 100 µm) reveal markedly higher IONP coating density on C. albicans biofilms following dabbing treatment. (C) Cell viability analysis showing limited killing of C. albicans cells by dispersed IONP treatment. Adapted from Ref [25] under the Creative Commons CC‐BY‐NC‐ND license. (D) Photomagnetic synergy enhances microrobot penetration through biological barriers. (E) Schematic and optical visualization of a rabbit sinusitis model demonstrating nanozyme robotic swarm penetration through biofilm and inflammatory secretions to reach the underlying sinus mucosa. Bright‐field and fluorescence imaging (red and green channels representing dead and live cells, respectively) illustrate inflammatory composition and time‐lapse tracking of swarm penetration under magnetic actuation. Adapted with permission from Ref [68] (Copyright 2025, The American Association for the Advancement of Science). (F) Schematic of the endoscope‐assisted biofilm eradication procedure using actuated Fe₂O₃ HMMs for tympanostomy tube disinfection. Top and cross‐sectional views of the T‐tube show biofilm morphology before and after treatment, with fluorescent imaging confirming efficient biofilm removal. Adapted from Ref [69] under a Creative Commons Attribution NonCommercial License 4.0 (CC BY‐NC).

FIGURE 6

Key directions toward advancing the potential of nanozyme microrobots for precision medicine.