Nanoparticles co-delivering α-mangostin and Lycium barbarum polysaccharide for dual antibacterial and anti-inflammatory therapy against bacterial infections

A novel nanoparticle (WSLM) encapsulating α-mangostin and Lycium barbarum polysaccharide for oral co-delivery. • WSLM effectively eradicates intracellular methicillin-resistant Staphylococcus aureus . • WSLM suppresses pro-inflammatory cytokines to alleviate the inflammatory response. • WSLM combats intestinal infection via integrated antibacterial and anti-inflammatory. Methicillin-resistant Staphylococcus aureus (MRSA) is a globally prevalent pathogen responsible for severe and often refractory gastrointestinal infections. Current therapeutic strategies predicated on bactericidal activity overlook the critical pathological consequence of bacterial lysis, which involves the release of cell components that trigger excessive host inflammatory responses and exacerbate intestinal injury. Inspired by the need for integrated host-pathogen modulation, we developed an oral co-delivery nanoparticle system (WSLM) based on chitosan and whey protein isolate, which encapsulates α-mangostin and Lycium barbarum polysaccharide, to enable coordinated antibacterial and anti-inflammatory intervention within the gastrointestinal tract. WSLM effectively inhibited MRSA biofilm formation and bacterial colonization while significantly attenuating infection-associated inflammation, reducing TNF-α and IL-6 levels by approximately 76.1% and 59.3%, respectively. In a mouse model of MRSA intestinal infection, oral administration of WSLM significantly alleviated intestinal pathology, restored colon length, and decreased bacterial load by approximately three orders of magnitude. Mechanistically, WSLM promoted epithelial barrier repair through the upregulation of tight junction proteins. Furthermore, microbiome analysis revealed that WSLM showed enrichment of beneficial commensal families, including Lachnospiraceae and Oscillospiraceae . Overall, this study has established a multifunctional nano-delivery system targeting bacterial infection and hyperinflammation simultaneously, providing an experimental paradigm for the treatment of bacterial intestinal infections. Download: Download high-res image (119KB) Download: Download full-size image