Nanoparticles Self-Assembled from Berberine and Chrysin for Generating Antimicrobial Films

Methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans (CA) are common pathogenic organisms in humans and pose a severe threat to public health. Coinfection of MRSA and CA often forms durable biofilms on abiotic surfaces or in the host, which is the main strategy for these pathogens to resist antibiotics and escape from host immune surveillance. However, the limited options of available antibiotics and the emergence of drug-resistant strains further increase the difficulty in treating microbial infections. Inspired by the clinical application of traditional herbal medicines, we prepare natural small molecule carrier-free binary nanoparticles (NPs), which are self-assembled from berberine and chrysin through a one-pot method. Interestingly, the pharmacologic mechanisms of the NPs against MRSA and CA are different. We show here that NPs plays an anti-MRSA effect by inducing cell death, while NPs inhibit CA by causing prolonged M phase progression, abnormal cytokinesis, diminished hyphal growth, and disturbed cell wall. Furthermore, NPs exhibit inhibition and eradication of mono- and dual-species biofilms of MRSA and CA. Given the excellent antimicrobial activities of NPs, the NPs show no obvious hemolytic and cytotoxicity, suggesting that they have desired clinical application value in the treatment coinfection of MRSA and CA.