Protective effect of curcumin-loaded zeolitic imidazolate framework-8-based pH-responsive drug delivery system against Staphylococcus aureus infection.

Mastitis, generally caused by pathogenic microorganisms, is a serious disease in dairy farming. Staphylococcus aureus (S. aureus) is one of the main pathogens that induces mastitis in dairy cows. It evades the innate and adaptive immune responses of dairy cows, causing recessive transmission and harming the health of the mammary glands. Antibiotics remain the primary treatment; however, their excessive use can lead to antimicrobial resistance. Therefore, it is necessary to develop new strategies to replace antibiotic therapies. The zeolitic imidazolate framework (ZIF-8) is a metal-organic skeleton material with applications in biology and drug delivery. This study aimed to construct a novel nanodrug delivery system for S. aureus infection by combining ZIF-8 with curcumin (ZIF-8@CCM), which exhibits antibacterial and anti-inflammatory properties. Bovine mammary epithelial cells (BMECs) and mice were used to evaluate the therapeutic efficacy and biotoxicity of the system, and to explore the protective mechanism of ZIF-8@CCM. The results showed that ZIF-8@CCM exhibited high drug loading capacity, stability, and pH responsiveness. Both in vitro and in vivo experiments revealed that ZIF-8@CCM effectively released encapsulated curcumin in response to the acidic microenvironment induced by bacterial infection, which in turn enhanced the bactericidal efficacy. It not only prevents biofilm formation, but also mitigates the toxic side effects associated with drug treatments, showing excellent bioavailability and biocompatibility. Furthermore, ZIF-8@CCM also attenuated S. aureus-induced inflammatory through suppressing the activation of TLR2-NF-κB pathway. Consequently, ZIF-8@CCM is an effective targeted antibacterial and anti-inflammatory drug, showing promise as a novel therapeutic agent for the clinical management of S. aureus-induced mastitis in dairy cows.