Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity

The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)-inducing Fe3+) were separately loaded in the yolk and shell compartment of a yolk-shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three-dimensional spherical biofilm model is novel and clinically relevant.

Automated summary

Heterogeneity in biofilms is a major challenge in biofilm therapies. This study presents a therapeutic strategy that overcomes biofilm heterogeneity by separately loading an antibacterial agent and an EPS dispersant in different compartments of a yolk-shell nanoplatform. The strategy takes advantage of the pharmacokinetic complementarity of ROS and NO to penetrate the biofilm and eliminate bacteria.