Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity
Xue Han, Qi Lou, Feng Feng, Guanhua Xu, Song Hong, Li Yao, Shijie Qin, Dazhuan Wu, Xiaoping Ouyang, Zhiguo Zhang, Xiuyu Wang
Abstract
Abstract 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 Fe 3+ ) 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.