DNA Nanostructures for Targeted Antimicrobial Delivery

Abstract

We report the use of DNA origami nanostructures, functionalized with aptamers, as a vehicle for delivering the antibacterial enzyme lysozyme in a specific and efficient manner. We test the system against Gram‐positive (Bacillus subtilis) and Gram‐negative (Escherichia coli) targets. We use direct stochastic optical reconstruction microscopy (dSTORM) and atomic force microscopy (AFM) to characterize the DNA origami nanostructures and structured illumination microscopy (SIM) to assess the binding of the origami to the bacteria. We show that treatment with lysozyme‐functionalized origami slows bacterial growth more effectively than treatment with free lysozyme. Our study introduces DNA origami as a tool in the fight against antibiotic resistance, and our results demonstrate the specificity and efficiency of the nanostructure as a drug delivery vehicle.

Nano-vehicles give new lease of life to existing antimicrobials

“…In this study, Mela et al exploited the potential for simultaneous multi-functionalisation of DNA origami by adding three functional components: aptamers that specifically bind to E. coli and Bacillus subtilis, the antimicrobial enzyme, and fluorophores to act as detection beacons for the nanostructures (Figure 3c). The nanostructures specifically bound to their bacterial targets, and the origami-bound lysozyme was more efficient at slowing bacterial growth than free lysozyme [82].…”

Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers

“…The use of aptamer functionalized DNA origami nanostructures for the delivery of antibacterial lysozyme was recently reported by Mela and colleagues [142]. Biotinylated staples were hybridized with DNA origami nanostructures consisting of a frame with five 'wells'.…”

“…Given the susceptibility of aptamers to enzymatic degradation by nucleases, delivery modalities and chemical modifications can improve their half-lives and stability in vivo. The use of aptamer functionalized DNA origami nanostructures for the delivery of antibacterial lysozyme was recently reported by Mela and colleagues [142]. Biotinylated staples were hybridized with DNA origami nanostructures consisting of a frame with five 'wells'.…”

“… ( A ) Schematic representation of DNA origami nanostructures featuring an aptamer, lysozyme and Alexa 647 fluorescence molecules. Image reproduced from [ 142 ]. Copyright John Wiley and Sons, 2020.…”

“…( B ) Average growth curves of E. coli in the presence of the lysozyme alone, origami alone and the lysozyme loaded origami nanostructures. Image reproduced from [ 142 ]. Copyright John Wiley and Sons, 2020.…”