Development of pH-responsive nanocomposites with remarkably synergistic antibiofilm activities based on ultrasmall silver nanoparticles in combination with aminoglycoside antibiotics

Abstract

Bacterial biofilms are responsible for many chronic infections because antibacterial agents exhibit poor penetration into the dense matrix barrier and cannot easily reach the internal bacteria. Herein, we reported pH-responsive nanocomposites (PDA@Kana-AgNPs) that could penetrate and disperse biofilms, which were synthesized by the combination of ultrasmall silver nanoparticles (AgNPs) and kanamycin, and then coating with polydopamine. Confocal fluorescence imaging indicated that PDA@Kana-AgNPs could respond to the acidic microenvironment of biofilms, leading to biofilm-triggered on- demand drug release in situ. The zone of inhibition test and Resazurin assay showed that the combination of kanamycin and AgNPs had greater antimicrobial activity against test strains (Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli BL21) than when applied separately. The crystal violet staining test demonstrated that biofilms were effectively dispersed by the proposed nanocomposites. Biocompatibility was also evaluated, which showed that PDA@Kana-AgNPs were non-toxic to mammalian cells. Therefore, the proposed pH-responsive nanocomposites held great potential for efficient antibiotics delivery and showed synergistic antibacterial and antibiofilm activities. This strategy could also be used to encapsulate a variety of antibiotics in combination with other drugs or materials, thereby showing therapeutic potential in preventing biofilm-related infections and realizing fluorescence imaging in situ.