The use of nanomaterials as antifungal agents has been investigated on several occasions, and although their potential was demonstrated, it was also found that they do not have the necessary specificity to develop an efficient antifungal function, resulting in longer treatments, unexpected side effects and increased drug resistance.

Professor Hyun Michel Koo

School of Dentistry and co-author of the study

Candida forms infectious biofilms that are particularly difficult to treat and for which current antifungal therapies lack the potency and specificity to eliminate.

Now, in this new study published in Advanced Materials under the title title Nanozyme-Based Robotics Approach for Targeting Fungal Infection, researchers from the University of Pennsylvania’s School of Dentistry and School of Engineering and Applied Sciences have developed magnetically controlled nanorobots to eradicate oral fungal infections quickly and accurately, providing a unique solution that would improve the efficacy of such treatments.

Dr Edward Steager, from the School of Engineering and Applied Sciences and co-investigator of the study, explains how the procedure works: “The nanoparticles are magnetically controlled, which allows us to direct them to the exact site of infection. As they are made of iron oxide, they have another important property: they are catalytic”.

In the presence of hydrogen peroxide, these catalytic nanoparticles (known as nanozymes) generate multiple oxygen-containing molecules that have an antimicrobial effect. They are also biocompatible, non-toxic and safe to use for therapeutic purposes.

Iron oxide nanoparticles (IONPs) have been used against bacterial pathogens associated with biofilm infections due to their high magnetic susceptibility. They also allow very precise dosing, making them a very attractive nanomaterial for biomedical applications.

Unexpectedly, the researchers found that the nanozyme assemblies bound to fungal (C. albicans) cells more specifically than to human (gingival) cells, and that this binding greatly enhanced the antifungal effect: by interacting, they acquired the ability to selectively kill the fungus.

The research team sees great future potential for their nanozyme-based microbots: while Dr Steager focuses on the magnetic particularity of the process, claiming that the binding “achieves a potent and concentrated antifungal effect that also does not affect other non-infected areas”, Prof Koo is enthusiastic about its potential for automation: “The magnetic and catalytic properties combined with an unexpected fungal binding specificity open up exciting opportunities for an automated antifungal mechanism.

How does it work?

By modulating the frequency of the electromagnetic field and small-scale spatio-temporal control, structured arrays of iron oxide nanoenzymes are formed that trigger catalytic activity to control the generation of reactive oxygen species (ROS).

In this way, the nanozymes bind to the surfaces of Candida albicans fungus, one of the most common and widespread fungal organisms causing human infections, in a concentrated form to selectively eliminate them.

This results in localised antifungal activity: nanozymes target infected sites with high precision and eradicate the fungus in a short time, providing a unique and effective therapeutic modality that minimises unwanted effects.

These findings could lead to high-precision nanozyme-based therapies for treating oral fungal infections, although detailed studies are needed to assess the binding affinity and adhesion mechanisms of nanozymes to fungal surfaces, as well as whether other microbes can be targeted in a similar way.