Enhanced chemodynamic porphyrin-modified magnetite nanoagents: A triple-action strategy for potent antimicrobial therapy and wound healing

Abstract

The rise of drug-resistant bacteria, including multidrug-resistant (MDR) strains, has exposed the limitations of current antibiotic treatments. Chemodynamic therapy (CDT) has emerged as a promising approach due to its ability to generate reactive oxygen species (ROS) through Fenton or Fenton-like reactions in infection microenvironments (IMEs). However, the short lifespan, limited diffusion range of ·OH, and restricted variety of ROS reduce the effect of CDT. This study developed amine porphyrins (TAPP)-functionalized Fe₃O₄ nanoparticles (Fe₃O₄@TAPP NPs) as a multifunctional antibacterial platform. The TAPP layer can not only trap bacteria through electrostatic attraction in acidic environments but also increase the localized heat upon near-infrared (660 nm) excitation, reducing the effective action distance and boosting the production rate of ·OH. Notably, TAPP was covalently bonded to Fe₃O₄ nanoparticles via its amine groups and the carboxylic groups on Fe₃O₄, preventing TAPP self-aggregation under physiological conditions, and preserving the PDT effect. Therefore, the TAPP layer on Fe₃O₄ nanoparticles performs three functions, resolving the three limitations simultaneously to enhance CDT in a triple-action strategy. The developed Fe₃O₄@TAPP NPs exhibit improved antibacterial efficiency both in vitro and in vivo. Overall, this study provides an innovative strategy to construct an antibacterial nanoplatform for synergistically enhanced CDT antibacterial treatment, exhibiting great potential for future biomedical applications.