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Overuse of antibiotics has led to multidrug resistance in bacteria, posing a tremendous challenge to the healthcare system. There is an urgent need to explore unconventional strategies to overcome this issue. Herein, for the first time, we report a capacitive Co 3 O 4 nanowire (NW) electrode coated on flexible carbon cloth, which is capable of eliminating bacteria while discharging, for the treatment of skin infection. Benefiting from the unique NW-like morphology, the Co 3 O 4 NW electrode with increased active sites and enhanced capacitive property exhibits a prominent antibacterial effect against both Gram-positive and Gram-negative bacteria after charging at a low voltage of 2 V for 30 min. Furthermore, the electrode is demonstrated to be recharged for multiple antibacterial treatment cycles without significant change of antibacterial activity, allowing for practical use in a non-clinical setting. More importantly, this Co 3 O 4 NW electrode is capable of damaging bacterial cell membrane and inducing the accumulation of intracellular reactive oxygen species without impairing viability of skin keratinocytes. In a mouse model of bacterial skin infection, the Co 3 O 4 electrode shows significant therapeutic efficacy by eradicating colonized bacteria, thus accelerating the healing process of infected wounds. This nanostructured capacitive electrode provides an antibiotic-free, rechargeable, and wearable approach to treat bacterial skin infection.

Background P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. Methods A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. Results Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. Conclusion The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.

Antibiotic-free antimicrobial strategies are urgently needed to address the rapid evolution of antimicrobial resistance and transmission of multidrug-resistance bacterial infections. Herein, we fabricated polydopamine-coated porous magnetic nanoparticles (pMNPs@PDA) for effective separation and photothermal killing of methicillin-resistant Staphylococcus aureus (MRSA). Taking advantage of the excellent bacteria-affinitive property of polydopamine, the nanoparticles were anchored on the surface of bacteria, permitting rapid and efficient MRSA capture and separation with over 99% removal via the application of a magnetic field in 30 min. It was found, for the first time, that polydopamine-coated magnetic nanoparticles displayed a selective capture of Gram-positive bacteria when compared with Gramnegative bacteria. The selectivity was attributed to the preferable binding capability of pMNPs@PDA to peptidoglycan (PGN) of Gram-positive bacteria, compared to the lipopolysaccharide (LPS) of Gram-negative bacteria. With the magnetic separation and photothermal properties, pMNPs@PDA exhibited efficient killing of the captured MRSA under the irradiation of near-infrared (NIR) light. Cell cytotoxicity testing demonstrated good biocompatibility of the nanoparticles. These antibiotic-free nanoparticles capable of fast capture, separation, and inactivation of MRSA may be potentially used for water disinfection, blood purification, and treatment of bacterial infections.

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