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

To address the issues of insufficient bacterial targeting and short hepatic retention associated with traditional antibiotic treatments for S. aureus 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 S. aureus 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 S. aureus 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 Staphylococcus aureus -induced liver infection. This approach represents an effective strategy for the targeted nanotherapy of deep-seated bacterial infections.