Nanozyme platform with built-in electric field and gas modulation for deep biofilm penetration and enhanced antibacterial therapy

Abstract

Migration of nanozymes along the microenvironmental gradient within biofilms represents a promising approach to disrupt their internal structure. However, the low catalytic activity of nanozymes in the biofilm microenvironment, combined with the dense and compact nature of biofilms, significantly restricts their ability to achieve effective biofilm penetration. Herein, we propose a strategy to enhance nanozyme activity while simultaneously disrupting biofilm extracellular polymeric substances (EPS) by incorporating the basic amino acid polymer, ε-polylysine/L-arginine (PLL-arg), into nanozyme (PLL-arg@MnO₂). The PLL-arg core acts as a proton reservoir, supplying the necessary protons for the catalytic reaction. The MnO₂ shell, together with the positively charged PLL-arg, generates an internal high and external low local electric field, which expels the reaction product Mn²⁺, thereby accelerating the reaction rate and enhancing nanozymes' mobility. Furthermore, nitric oxide (NO) released in response to hydrogen peroxide (H₂O₂) effectively reduces biofilm density, enabling nanozymes to penetrate deeper into the biofilm interior. Upon penetrating the biofilm interior, the integration of oxygen generation, NO release, and antimicrobial peptide functionality within the nanozymes facilitates synergistic antibacterial effects, effectively implementing “penetrating + treating” strategies. Biofilm experiments exhibit that the nanozymes achieve a therapeutic depth of 85.71% of the entire biofilm. This work provides a template for developing nanozymes that target and penetrate biofilms.