Honokiol-loaded nanoparticles for targeted bacterial eradication and treatment of MRSA infection

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections and the formation of associated biofilms often lead to refractory and recurrent bacterial infections, posing a serious threat to public health. Herein, a pH-responsive antibiotic-free nanoparticle (HNK@RHL-COS NPs) was prepared by encapsulating the natural antimicrobial agent honokiol (HNK) with rhamnolipid-modified chitosan, enabling targeted disassembling at the acidic infection site, destruction of the biofilm by rhamnolipid, thereby enhancing the penetration of honokiol and chitosan, thus achieving their synergistic bactericidal effect. HNK@RHL-COS NPs exhibited enhanced antimicrobial effects against MRSA, with a minimum inhibitory concentration (MIC) value of 2 μg/mL, significantly inhibited the formation of biofilm and eradicated the mature biofilm. Furthermore, HNK@RHL-COS NPs efficiently accelerated the healing of wounds in MRSA-infected mice, alleviated bacterial peritonitis in mice, and demonstrated excellent biocompatibility <i>in vitro</i> and <i>in vivo</i>. Collectively, this study provides a novel and safety solution for the clinical treatment of MRSA infections.