Due to their resistance to current treatments, fungus-caused infections like Candida albicans pose a significant threat to global health, to the point where the World Health Organization has designated this as a top priority.
The current iterations of nanomaterials lack the potency and specificity required for quick and targeted treatment, despite their potential as antifungal agents. This results in prolonged treatment times, potential off-target effects, and drug resistance.
A team of researchers led by Hyun (Michel) Koo from the University of Pennsylvania School of Dental Medicine and Edward Steager from Penn’s School of Engineering and Applied Science has developed a microrobotic system that is capable of rapidly and precisely eliminating fungal pathogens, a groundbreaking development that has far-reaching implications for global health.
“Candidae forms tenacious biofilm infections that are extremely difficult to treat. Current antifungal medications lack the potency and specificity needed to remove these organisms rapidly and efficiently, so our cooperation combines our clinical experience with Ed’s team and their robotic expertise to give a new approach.”
Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine.
“Candidae structure steady biofilm diseases that are especially difficult to treat,” Koo says. “This collaboration combines Ed’s team’s robotic expertise with our clinical knowledge to provide a novel strategy because current antifungal therapies lack the potency and specificity required to quickly and effectively eradicate these pathogens.
The group of researchers is a part of Penn Dental’s Center for Innovation and Precision Dentistry, a project that uses engineering and computational methods to find new information that can help prevent disease and advance new ideas for oral and craniofacial health care.
The researchers built miniature robotic systems that were able to precisely target and rapidly destroy fungal cells for this paper, which was published in Advanced Materials. They took advantage of recent advancements in catalytic nanoparticles, which are also known as nanozymes. They were able to accomplish this by precisely controlling the shape and movements of these nanozyme microrobots through the use of electromagnetic fields.
Steager explains, “The magnetic methods we use to control the nanoparticles in this study allow us to direct them to the exact location of the infection.” We utilize iron oxide nanoparticles, which have another significant property, in particular that they’re reactants.”
The array of nanozyme bots precisely follows magnetic cores as they head for the fungal infection site. Credit: Min Jun Oh and Seokyoung Yoon.
The nanozyme motion, velocity, and formations developed by Steager’s group enhanced the enzyme’s catalytic activity, similar to how the enzyme peroxidase breaks down hydrogen peroxide into water and oxygen. This directly makes it possible to produce a lot of reactive oxygen species (ROS), which are compounds that have been shown to break up biofilms, at the infection site.
The motion, velocity, and formations of nanozymes were developed by the team of Min Jun Oh and Seokyoung Yoon Steager. This increased the enzyme’s catalytic activity, similar to how the enzyme peroxidase breaks down hydrogen peroxide into water and oxygen. This straightforwardly permits the accumulation of high levels of receptive oxygen species (ROS), which have demonstrated biofilm-annihilating properties, at the site of disease.
However, an unanticipated discovery was the truly ground-breaking aspect of these nanozyme assemblies: their high affinity for binding to fungal cells. “This property enables targeted ROS generation and a localized accumulation of nanozymes precisely where the fungi reside.” Steager says, “Our nanozyme assemblies have a remarkable attraction for fungal cells, especially when compared to human cells.” “A potent and concentrated antifungal effect without affecting other uninfected areas is made possible by this specific binding interaction.”
This, in conjunction with the inherent maneuverability of the nanozyme, produces a potent antifungal effect that demonstrates the rapid elimination of fungal cells within an unprecedented 10-minute window.
The team sees the potential of this one-of-a-kind nanozyme-based robotics strategy going forward as they incorporate new approaches to automate nanozyme control and delivery. Its potential for antifungal treatment is only the beginning. Its exact focus and fast activity suggest potential for treating different kinds of difficult contaminations.
Koo states, “We’ve discovered a powerful tool in the fight against pathogenic fungi.” Even though this is a significant step forward, it is only the first step. The attractive and reactant properties, combined with an unforeseen restricting particularity to parasites, open energizing doors for a computerized ‘target-tie and kill’ antifungal system. We are anxious to dig further and open its maximum capacity.”
This mechanical technology approach opens up another frontier in the battle against contagious diseases and imprints a critical point in antifungal treatment. Medical and dental professionals are closer than ever to successfully combating these difficult pathogens thanks to a new tool in their arsenal.
More information: Min Jun Oh et al, Nanozyme‐based robotics approach for targeting fungal infection, Advanced Materials (2023). DOI: 10.1002/adma.202300320
