Polymyxin B stabilized DNA micelles for sustained antibacterial and antibiofilm activity against P. aeruginosa

Nucleic acid-based materials showcase an increasing potential for antimicrobial drug delivery. Although numerous reports on drug-loaded DNA nanoparticles outline their pivotal antibacterial activities, their potential as drug delivery systems against bacterial biofilms awaits further studies. Among different oligonucleotide structures, micellar nanocarriers derived from amphiphilic DNA strands are of particular interest due to their spontaneous self-assembly and high biocompatibility. However, their clinical use is hampered by structural instability upon cation depletion. In this work, we used a cationic amphiphilic antibiotic (polymyxin B) to stabilize DNA micelles destined to penetrate P. aeruginosa biofilms and exhibit antibacterial/antibiofilm properties. Our study highlights how the strong affinity of this antibiotic enhances the stability of the micelles and confirms that antibacterial activity of the novel micelles remains intact. Additionally, we show that PMB micelles can penetrate P. aeruginosa biofilms and impact their metabolic activity. Finally, PMB micelles were highly safe and biocompatible, highlighting their possible application against P. aeruginosa biofilm-colonized skin wounds.

Automated summary

Nucleic acid-based materials have great potential for antimicrobial drug delivery. This study focuses on the stability and antibacterial properties of micellar nanocarriers derived from amphiphilic DNA strands against bacterial biofilms. By using a cationic amphiphilic antibiotic, the stability of the micelles is enhanced, their antibacterial activity remains intact, and they can penetrate bacterial biofilms and impact their metabolic activity. The PMB micelles are also highly safe and biocompatible, making them suitable for application against P. aeruginosa biofilm-colonized skin wounds.