Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment

Abstract Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities for Staphylococcus aureus ( S. aureus ). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity against S. aureus . Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF- α , IL-6, and IL-1 β from macrophage inflammatory cells. This was achieved through downregulating the activation of NF- κ B, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth of S. aureus in the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.