Potassium-Doped MnO₂ Nanoparticles Reprogram Neutrophil Calcium Signaling to Accelerate Healing of Methicillin-Resistant <i>Staphylococcus aureus</i>-Infected Diabetic Wounds

Abstract

High Resolution Image Download MS PowerPoint Slide Neutrophils, as first-line immune cells, typically lose their edge within the diabetic wounds accompanied by methicillin-resistant Staphylococcus aureus (MRSA) infections (the D/M setting), playing the role of “more foe than friend” during the healing process. Specifically, reduced influx of calcium ions (Ca 2+ ) and impaired calcium homeostasis yield the dysfunction of neutrophil sequential behaviors in pathogen killing and wound healing, manifesting as suppressed chemotaxis, decreased intracellular reactive oxygen species (ROS) generation, prolonged apoptosis, and retention of neutrophil extracellular traps (NETs). To address this challenge, this study fabricated potassium (K)-doped manganese dioxide nanoparticles (MnO 2 NPs), which activated transmembrane Ca 2+ channels by inducing neutrophil depolarization via electron transfer. Subsequently, this contributed to the initial Ca 2+ influx and reprogrammed Ca 2+ -dependent behaviors of impaired neutrophils. Also, the potential antimicrobial capacity of K-MnO 2 NPs created a favorable extracellular environment that restored calcium homeostasis, enabling apoptotic neutrophils to be removed timely. Therefore, the wounds treated with K-MnO 2 NPs in the D/M setting exhibited potent resistance to MRSA and rapid healing, which could be attributed to the synergistic effects of K-MnO 2 NPs in leveraging Ca 2+ influx and maintaining calcium homeostasis. In brief, K-MnO 2 NPs constitute an effective strategy to resist MRSA and rapid wound healing in the D/M setting.