Tetrahedral Framework Nucleic Acids Deliver Antimicrobial Peptides with Improved Effects and Less Susceptibility to Bacterial Degradation

Antimicrobial peptides (AMPs) have been an attractive alternative to traditional antibiotics. However, considerable efforts are needed to further enhance their antimicrobial effects and stability against bacterial degradation. Tetrahedral framework nucleic acids (tFNAs), a new class of three-dimensional nanostructures, have been utilized as a delivery vehicle. In this study, tFNAs were combined for the first time with an antimicrobial peptide GL13K, and the effects of the resultant complexes against Escherichia coli (sensitive to GL13K) and Porphyromonas gingivalis (capable of degrading GL13K) were investigated. tFNA-based delivery enhanced the effects of GL13K against E. coli. The tFNA vehicle both increased bacterial uptake and promoted membrane destabilization. Moreover, it enhanced the effects of GL13K against P. gingivalis by protecting the peptide against degradation in the protease-rich extracellular environment. Therefore, tFNA provides a delivery vehicle for AMPs targeting a broad range of disease.