Microbubble-driven nanoparticles deliver gene suppressors to break down MRSA biofilms

A major cause of hospital-acquired infections, the super bacteria Methicillin-resistant Staphylococcus aureus (MRSA), not only exhibits strong resistance to existing antibiotics but also forms a dense biofilm that blocks the effects of external treatments.

To meet this challenge, KAIST researchers, in collaboration with an international team, successfully developed a platform that utilizes microbubbles to deliver gene-targeted nanoparticles capable of breaking down the biofilms, offering an innovative solution for treating infections resistant to conventional antibiotics.

A research team led by Professor Hyun Jung Chung from the Department of Biological Sciences, in collaboration with Professor Hyunjoon Kong’s team at the University of Illinois, has developed a microbubble-based nano-gene delivery platform (BTN MB) that precisely delivers gene suppressors into bacteria to effectively remove biofilms formed by MRSA.

The study was published in the journal Advanced Functional Materials.

The research team first designed short DNA oligonucleotides that simultaneously suppress three major MRSA genes, related to—biofilm formation (icaA), cell division (ftsZ), and antibiotic resistance (mecA)—and engineered nanoparticles (BTN) to effectively deliver them into the bacteria.

In addition, microbubbles (MB) were used to increase the permeability of the microbial membrane, specifically the biofilm formed by MRSA. By combining these two technologies, the team implemented a dual-strike strategy that fundamentally blocks bacterial growth and prevents resistance acquisition.

This treatment system operates in two stages. First, the MBs induce pressure changes within the bacterial biofilm, allowing the BTNs to penetrate.

Then, the BTNs slip through the gaps in the biofilm and enter the bacteria, delivering the gene suppressors precisely. This leads to gene regulation within MRSA, simultaneously blocking biofilm regeneration, cell proliferation, and antibiotic resistance expression.

In experiments conducted in a porcine skin model and a mouse wound model infected with MRSA biofilm, the BTN MB treatment group showed a significant reduction in biofilm thickness, as well as remarkable decreases in bacterial count and inflammatory responses.

These results are difficult to achieve with conventional antibiotic monotherapy and demonstrate the potential for treating a wide range of resistant bacterial infections.

Professor Hyun Jung Chung of KAIST, who led the research, stated, “This study presents a new therapeutic solution that combines nanotechnology, gene suppression, and physical delivery strategies to address superbug infections that existing antibiotics cannot resolve. We will continue our research with the aim of expanding its application to systemic infections and various other infectious diseases.”

The study was co-first authored by Ju Yeon Chung, a graduate student in the Department of Biological Sciences at KAIST, and Dr. Yujin Ahn from the University of Illinois.