Light-activated copper microrobots use single-atom catalysis and peroxide to penetrate biofilms, generate reactive oxygen species, and eliminate MRSA infections.
(Nanowerk Spotlight) Bacterial biofilms pose one of the most intractable challenges in medicine. These tightly organized microbial communities adhere to surfaces such as wound beds, catheters, and implants. Encased in a dense protective matrix, biofilms create a physical and chemical barrier that reduces the effectiveness of antibiotics and shields the bacteria from immune cells. Methicillin-resistant Staphylococcus aureus (MRSA), a particularly aggressive and resilient strain, is known to thrive in such environments. Once established, MRSA biofilms can persist even under intensive antimicrobial treatment, leading to chronic infections, delayed healing, and systemic complications.
Attempts to treat biofilm-related infections have long struggled with one core issue: limited penetration. Traditional antibiotics are designed to act on planktonic (free-floating) bacteria, but they often fail to reach the cells embedded deep within biofilms. Over the past two decades, researchers have explored a range of alternatives including enzyme-based dispersal agents, nanoparticle drug carriers, and surface coatings that release antimicrobials. While these strategies have yielded incremental improvements, most depend on passive diffusion and lack directional control. As a result, they often fall short when facing mature biofilms that are spatially structured and metabolically heterogeneous.
A more recent approach has focused on harnessing the unique reactivity of single-atom catalysts (SACs). These materials mimic natural enzymes but are composed of isolated metal atoms anchored to a supporting matrix. Their high surface-area-to-volume ratio allows them to convert molecules like hydrogen peroxide (H₂O₂) into reactive oxygen species (ROS)—highly reactive chemical forms that can degrade biofilms and damage bacterial membranes. SACs have shown promise in lab studies, but their reliance on passive dispersion has continued to limit their clinical potential.
Parallel advances in microrobotics have opened up new avenues. Tiny engineered machines capable of moving autonomously at micro- or nanoscale can actively navigate through biological fluids and tissues. Researchers have used magnetic fields, ultrasound, or catalytic reactions to power these systems, but integrating catalytic function with propulsion in a single, responsive structure remains a major technical challenge.
A study from the State Key Laboratory of Flexible Electronics and the Institute of Advanced Materials at Nanjing University of Posts and Telecommunications addresses this challenge by combining SACs with an actively motile microrobot platform. As they report in Advanced Functional Materials (“One-End-Opened Yolk–Shell Copper Single-Atom Microrobots for Enhanced Penetration and Eradication of Bacterial Biofilms”), the team developed a copper-based single-atom microrobot designed for targeted biofilm penetration and disinfection.
The system, known as Y-CuSA/CN, is built with a one-end-opened yolk–shell structure. Copper atoms are dispersed at the atomic level on a carbon nitride support, forming Cu–N₄ coordination sites. This configuration supports both catalytic and photoreactive activity. When exposed to UV light, the carbon nitride matrix generates excited electrons. These electrons participate in redox cycling of the copper sites and accelerate the decomposition of hydrogen peroxide into ROS such as hydroxyl radicals (·OH), superoxide radicals (·O₂⁻), and singlet oxygen (¹O₂).
The microrobot’s asymmetric geometry plays a critical role in its motion. According to the figure below, the closed yolk cavity, rich in copper sites, becomes a catalytic hub, consuming H₂O₂ more rapidly than the open end. This creates a self-sustaining chemical gradient across the particle, driving movement from areas of high H₂O₂ concentration toward low. The result is directional propulsion powered by chemical energy, known as self-diffusiophoresis. Under combined UV illumination and H₂O₂ exposure, the microrobots reached an average velocity of 17.2 micrometers per second and exhibited diffusion coefficients six times greater than passive particles .
Schematic representation of Cu single-atommicrorobots (Y-CuSA/CN) for enhanced penetration and eradication of MRSA bacterial biofilms. (Image: Reprinted with permission by Wiley-VCH Verlag) (click on image to enlarge)
Comparative tests confirmed that this behavior depends on both structural design and dual-mode activation. A symmetric version of the microrobot, lacking the yolk–shell geometry, showed significantly weaker propulsion. Motion also diminished when either UV light or hydrogen peroxide was removed. In combination, the catalytic and optical components yielded enhanced and sustained movement through fluid environments. According to the team, only the dual-driven microrobots achieved extended paths suitable for navigating through complex tissue or biofilm structures.
The researchers evaluated the system’s antibacterial effects using both Gram-negative (E. coli) and Gram-positive (MRSA) strains. Within 30 minutes of treatment under dual activation, the Y-CuSA/CN microrobots eliminated viable bacteria in both types of biofilms. Scanning electron microscopy revealed that untreated biofilms retained their dense, intact structure, while those exposed to the microrobots showed significant disruption and cell loss. Crystal violet staining and absorbance measurements indicated that the microrobots removed up to 87% of the biofilm biomass. Live/dead fluorescence imaging further confirmed extensive bacterial cell death throughout the biofilm volume .
Beyond disinfection, the study addressed the system’s compatibility with biological tissues. Cytotoxicity tests using human endothelial cells showed that the microrobots maintained over 85% cell viability at therapeutic doses. Hemolysis tests confirmed that the materials were non-damaging to red blood cells. Additionally, the microrobots promoted endothelial cell migration in wound models, a critical step in tissue regeneration. These findings support the use of Y-CuSA/CN in clinical settings, where both safety and functional compatibility are essential .
To test the therapeutic performance in vivo, the team created a mouse model of MRSA-infected wounds. Mice were given standardized skin wounds and inoculated with MRSA to form mature biofilms. Treatments were administered on alternating days and included various combinations of microrobots, UV light, and hydrogen peroxide. Only the group receiving the full combination showed near-complete wound closure by day 8, with wound area reduced to 9% of the original. Bacterial load was reduced by five orders of magnitude compared to controls. Tissue histology showed lower inflammation, increased collagen deposition, and greater blood vessel formation in the treated group.
Page 9 of the study includes immunohistochemical analyses of wound tissue. Vascular endothelial growth factor (VEGF), a key signal for angiogenesis, was elevated fivefold in the treated group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly suppressed, suggesting not only microbial clearance but also modulation of the wound healing environment. Immunofluorescence staining revealed dense networks of nascent and mature microvessels, indicating that the treatment supported both immediate disinfection and long-term tissue repair .
The mechanism underlying this activity was investigated using specific fluorescent probes and electron spin resonance spectroscopy. The researchers showed that hydroxyl radicals, superoxide radicals, and singlet oxygen were all produced at higher levels under UV and H₂O₂ conditions. This reactive environment enables the microrobots to degrade extracellular biofilm matrix components and compromise bacterial membranes. The catalytic sites remained active through redox cycling, allowing sustained ROS production during motion.
The Y-CuSA/CN microrobot system demonstrates that directional propulsion and single-atom catalysis can be integrated to overcome the spatial and chemical defenses of bacterial biofilms. It addresses key limitations of both traditional antibiotics and passive nanoparticle therapies by actively navigating to infection sites and maintaining localized chemical activity.
This work suggests that microrobotic platforms can be engineered not just for targeted delivery, but as active therapeutic agents in their own right. By coupling motion, catalysis, and biological compatibility, the system moves beyond the constraints of passive treatment paradigms. While further research is needed to assess performance in larger models and under clinical conditions, the study provides a framework for developing autonomous microdevices capable of treating resistant infections and supporting tissue healing in parallel.
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