Nanorobotic systems present new options for targeting fungal infections

Infections caused by fungi, eg candida albicanspose a significant global health risk due to their resistance to existing treatments, so much so that the World Health Organization is highlighting this as a priority issue.

Infections caused by fungi, eg candida albicanspose a significant global health risk due to their resistance to existing treatments, so much so that the World Health Organization is highlighting this as a priority issue.

Although nanomaterials show promise as antifungal agents, current iterations lack the potency and specificity required for rapid and targeted treatment, leading to long treatment times and the potential for adverse effects and drug resistance.

Now, in an innovative development with far-reaching implications for global health, a team of researchers co-led by Hyun (Michel) Koo of the University of Pennsylvania School of Dentistry and Edward Steager of Penn’s School of Engineering and Applied Science have created a microrobot system capable of eliminating fungal pathogens by fast and targeted.

“Candidae form biofilm infections that are difficult to treat,” says Koo. “Current antifungal therapies lack the potency and specificity needed to eliminate this pathogen quickly and effectively, so this collaboration draws on our clinical knowledge and combines Ed’s team and their robotic expertise to offer a new approach.”

The research team is part of Penn Dental’s Center for Innovation & Precision Dentistry, an initiative that leverages engineering and computational approaches to uncover new knowledge for disease mitigation and advance oral and craniofacial healthcare innovation.

For this paper, published in Advanced Materials, the researchers took advantage of recent advances in catalytic nanoparticles, known as nanozymes, and they built a miniature robotic system that can accurately target and rapidly destroy fungal cells. They achieve this by using electromagnetic fields to control the shape and movement of these micro-nanozyme robots with extreme precision.

“The method we used to control the nanoparticles in this study is magnetic, which allows us to direct them to the precise site of infection,” said Steager. “We used iron oxide nanoparticles, which have another important property, which is that they are catalytic.”

Steager’s team developed the motion, speed, and formation of nanozymes, which resulted in increased catalytic activity, such as peroxidase enzymes, which help break down hydrogen peroxide into water and oxygen. This directly allows the formation of high amounts of reactive oxygen species (ROS), compounds that have been shown to damage biofilms, at sites of infection.

However, the real pioneering element of this nanozyme assembly was an unexpected discovery: its strong binding affinity for fungal cells. This feature allows localized accumulation of nanozymes right where the fungus is located and, consequently, targeted generation of ROS.

“Our nanozyme assembly showed remarkable traction in fungal cells, especially when compared to human cells,” said Steager. “This specific binding interaction paves the way for a potent, concentrated antifungal effect without affecting other uninfected areas.”

Coupled with the inherent maneuverability of nanozymes, it produces a strong antifungal effect, demonstrating unprecedented rapid eradication of fungal cells within 10 minutes.

Looking ahead, the team sees the potential for this unique nanozyme-based robotics approach, as they incorporate new methods to automate the control and delivery of nanozymes. Promises for antifungal therapy are just the beginning. Its precise targeting, rapid action shows potential for treating other types of stubborn infections.

“We have discovered a powerful tool to combat pathogenic fungal infections,” said Koo. “What we have achieved here is a significant leap forward, but it is also only the first step. The magnetic and catalytic properties combined with the unexpected binding specificity to fungi open up exciting opportunities for automated ‘target-bind-and-kill’ antifungal mechanisms. We want to dig deeper and unlock its full potential.”

This robotics approach opens new frontiers in the fight against fungal infections and marks an important point in antifungal therapy. With a new tool in their arsenal, medical and dental professionals are closer than ever to effectively combating these difficult pathogens.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health and co-founder of the Center for Innovation & Precision Dentistry in the School of Dentistry at the University of Pennsylvania.

Edward Steager is a research investigator in the Robotics, Automation, Sensing & Perception General Laboratory in the School of Engineering and Applied Science at Penn.

Other authors include Min Jun Oh, Alaa Babeer, Yuan Liu, Zhi Ren, Zhenting Xiang, Yilan Miao, and Chider Chen of Penn Dental; and David P. Cormode and Seokyoung Yoon of the Perelman School of Medicine.

This research was supported in part by the National Institute for Dental and Craniofacial Research (R01 DE025848, R56 DE029985, R90DE031532 and; Basic Science Research Program through the National Research Foundation of Korea of ​​the Ministry of Education (NRF-2021R1A6A3A03044553).

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