Biomineralized nanozymes remodel the infectious microenvironment for precision MRSA pneumonia therapy.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia remains clinically challenging because antibiotic monotherapy is often insufficient to eradicate bacteria at pulmonary lesions and fails to resolve infection-amplified oxidative and inflammatory injury. Herein, we report a neutrophil membrane-cloaked, melanin-biomineralized MnO2 nanozyme platform co-loaded with curcumin and vancomycin (VC@NMM) for targeted antibacterial and immunoregulatory therapy of MRSA pneumonia. Through melanin-mediated biomineralization with KMnO4, a biocompatible MnO2 nanozyme framework is constructed with abundant interfacial sites for dual-drug loading and catalytic microenvironment regulation. In this integrated system, vancomycin directly inhibits MRSA growth, curcumin potentiates antibacterial activity and attenuates oxidative inflammation, and the MnO2 nanozyme mediates ROS scavenging, H2O2 decomposition, oxygenation improvement, and bacterial disruption. Neutrophil membrane cloaking further confers prolonged circulation and inflammation-tropic accumulation at MRSA-colonized lung tissues. Consequently, VC@NMM effectively reduces the required vancomycin dosage, disrupts bacterial integrity, induces protein leakage, impairs ATP metabolism, and suppresses MRSA survival in vitro. In MRSA pneumonia mouse model, VC@NMM significantly reduces pulmonary bacterial burden, alleviates edema and histopathological injury, inhibits ROS/NF-κB inflammatory signaling, remodels macrophage polarization, and prolongs survival. Collectively, this work establishes a biomineralized biomimetic nanozyme strategy that couples targeted antibiotic delivery with catalytic microenvironment remodeling and inflammation resolution for effective bacterial pneumonia therapy.