Fenton-catalytic nanocomposites for reprograming macrophages towards the improved anti-biofilm activity

Abstract

Abstract Bacterial infections involving the formation of biofilms are associated with diminished bactericidal activity of macrophages, which has been shown to contribute to the persistence in chronic infection. We recently reported that S. aureus biofilm-induced impairment of bactericidal activities of macrophages are associated with attenuation of reactive oxygen species (ROS) generation and NF-κB activation. The objective of this study is to validate the use of biocompatible Fenton-catalytic nanocomposites composed of iron oxide nanoparticles (IONPs), a reducing agent (ascorbic acid), and hydrogen peroxide (H2O2) to take advantage of their ability to stimulate the generation of ROS and activation of NF-kB in macrophages by means of triggering a Fenton reaction. Using an in vitro culture model of NF-kB reporter-RAW 264.7 macrophages, we optimized the range of the concentrations of IONPs, ascorbic acid, and/or H2O2, along with their respective combinations, exhibiting an enhanced NF-kB activity and ROS generation. Based on the findings, we subsequently validated the effect of nanocomposite on the bactericidal activity of macrophages exposed to S. aureus biofilm. Our results revealed that RAW 264.7 cells treated with IONPs resulted in significant reduction in the number of surviving bacteria by ~50% and its efficacy further increased in combination with ascorbic acid and/or H2O2, which were in line with the extent of NF-kB activation and ROS generation. In summary, our study supports that harnessing the characteristic of Fenton-catalytic nanocomposite to tune macrophage polarization to exhibit a bactericidal activity may provide a new strategy for treating infectious diseases. Funding support: Supported by NIH R01 NR 015674