Oleanolic acid-taxifolin self-assembled nanoparticles for effective treatment of S. aureus infections by inhibiting its internalization and reproduction

The intracellular parasitic traits of Staphylococcus aureus (S. aureus) facilitate its evasion of both antibiotic therapies and the host immune response, frequently resulting in therapeutic failures. Herein, using oleanolic acid (OA) and taxifolin (TAX) as raw ingredients, we developed self-assembled nanoparticles (OA-TAX NPs) with the goal to resolve an intracellular infection caused by S. aureus. OA-TAX NPs prohibited the invasion of S. aureus into cells by inhibiting sortase A (SrtA) activity and achieved intracellular effective accumulation through endocytosis. Specifically, OA-TAX NPs killed up to 84.4 % of intracellular S. aureus and alleviated inflammation. In the mice mastitis model, OA-TAX NPs successfully cured the S. aureus infection, improved the polarization of M2-type macrophages and dramatically reduced inflammatory damage. Overall, Antibiotic-free OA-TAX NPs offered an innovative strategy for the management of intracellular S. aureus.