Biofilm‐Sensitive Photodynamic Nanoparticles for Enhanced Penetration and Antibacterial Efficiency

Efficient antimicrobials are urgently needed for the treatment of bacterial biofilms due to their resistance to traditional drugs. Photodynamic therapy (PDT) is a new strategy that has been used to combat bacteria and biofilms. Cationic photosensitizers, particularly cationic photodynamic nanoagents, are usually chosen to enhance photodynamic antimicrobial activity. However, positively charged nanoparticles (NPs) are beneficial to cellular internalization, which causes increased cell cytotoxicity. Herein, a pH‐sensitive photodynamic nanosystem is designed. Rose Bengal (RB) polydopamine (PDA) NPs are decorated in a layer‐by‐layer fashion with polymyxin B (PMB) and gluconic acid (GA) to generate functionally adaptive NPs (RB@PMB@GA NPs). RB@PMB@GA NPs remain negative at physiological pH and exhibit good biocompatibility. When RB@PMB@GA NPs are exposed to an acidic infectious environment, the surface charge of the NPs is, in turn, positively charged as a result of pH‐sensitive electrostatic interactions. This surface charge conversion allows the RB@PMB@GA to effectively bind to the surfaces of bacteria and enhance photoinactivation efficiency against gram‐negative bacteria. Most importantly, RB@PMB@GA NPs exhibit good biofilm penetration and eradication under acidic conditions. Furthermore, RB@PMB@GA NPs efficiently eliminate biofilm infections in vivo. This study provides a promising strategy for safely treating biofilm‐associated infections in vivo. A pH‐sensitive photodynamic nanosystem is proposed. RB@PMB@GA nanoparticles (NPs) remain negatively charged at physiological pH and convert to be positively charged NPs in an acidic infectious environment. The conversion of the surface charge allows the NPs to effectively bind to the surfaces of negatively charged bacteria and significantly enhance their penetration and antibacterial photodynamic efficiency in biofilms of gram‐negative bacteria.