Catechol-Chitosan Nanoparticles Enable Iron Starvation and Bacterial Affinity for Targeted Hepatic Clearance of <i>Staphylococcus aureus</i>

To address the issues of insufficient bacterial targeting and short hepatic retention associated with traditional antibiotic treatments for <i>S. aureus</i> infections, this study developed lipid nanoparticles loaded with doxycycline (DX) using catechol-modified chitosan (CSC) and soybean phospholipid (PC) through a self-assembly process (DX@CSCNP, with a particle size of approximately 150 nm and an encapsulation efficiency greater than 85%) to evaluate their antibacterial efficacy. The constructed nanocarrier, following the incorporation of DX, exhibited enhanced colloidal stability. In vitro experiments demonstrated that the minimum inhibitory concentration (MIC) of DX@CSCNP was significantly lower than that of doxycycline hydrochloride, rapidly achieving bacterial eradication of <i>S. aureus</i> within 2 h. This effect was mediated by a dual mechanism involving the induction of bacterial iron starvation and enhanced bacterial affinity. In vivo distribution studies revealed that DX@CSCNP displayed significant accumulation and prolonged retention in the liver. In a mouse model of <i>S. aureus</i> infection, DX@CSCNP significantly reduced the bacterial load in the liver compared to free drug treatment, with noticeable improvements in liver appearance and histological evaluations. In conclusion, this study constructed a synergistic nanodelivery system integrating catechol-mediated bacterial targeting, prolonged hepatic retention, and phospholipid-enhanced drug release for enhanced treatment of <i>Staphylococcus aureus</i>-induced liver infection. This approach represents an effective strategy for the targeted nanotherapy of deep-seated bacterial infections.