Multifunctional ZnFeO4-Based Antibiotic Cross-Linked Nanoplatform for Magnetically Targeted Treatment of Microbial Biofilms

Abstract

During the infections of wounds or medical device surfaces, bacteria such as Pseudomonas aeruginosa are prone to forming biofilms which prevent the penetration of antimicrobial agents. Herein, a combined therapy using bactericidal nano-micelles Ce6-ZnFeO4@ABCsi-micelles was developed that employed colistin cross-linked Pluronic micelles as a carrier, with the magnetic metal oxide ZnFeO4 and photosensitizer dihydroporphyrin (Ce6) encapsulated in the core of micelles. Driven by an external magnetic field, the nano-micelles could penetrate the external barrier of the biofilm. Reactive oxygen species (ROS) generated by the photosensitizer Ce6 disrupted the barrier of the biofilm, which facilitated the distribution of the Ce6 and colistin antibiotics into the biofilm, realizing a 99.5% clearance rate of bacteria. Using such a combination of chemotherapy and photodynamic therapy, Ce6-ZnFeO4@ABCsi-micelles could clear wound infection in a murine abscess model, owing to the targeted driving effect of the external magnetic field, along with the chemotherapeutic effect of colistin and the photodynamic effect of Ce6. This design provides an effective targeted therapeutic strategy to address biofilm infections.