Self-Assemblies Based on Traditional Medicine Berberine and Cinnamic Acid for Adhesion-induced Inhibiting Multidrug-Resistant Staphylococcus aureus.

Along with S. aureus is being resistant to various first-line antibiotics, seeking multifarious strategies aimed at effective control of antibiotic-resistant behavior is urgent. Here, we report a two-component directed self-assembly mode: phytochemicals berberine and cinnamic acid can directly self-assemble into nanoparticles (NPs) displaying well bacteriostastic activity. Compared with several first-line antibiotics, the obtained nanostructures have better inhibitory effect on multidrug-resistant S. aureus (MRSA) and stronger ability to biofilm removal. These are attributed to that organic assemblies can firstly spontaneously adhere to the surface of bacteria, then infiltrate into cell, and lead to converging attack against MRSA; thereafter, multipath bactericidal mechanisms of NPs on MRSA are found by both transcriptomic analysis and quantitative Polymerase Chain Reaction (qPCR) analysis. Moreover, combining with spectral data and single crystal X-ray diffraction, NPs' self-assemble mechanism governed by hydrogen bonds and π-π stacking interactions is clearly elucidated. These non covalent interactions induce the NPs' formation of butterfly-like one-dimensional self-assembled units and finally layered three-dimensional spatial configuration. In addition, biocompatibility tests display that NPs is non-hemolytic, little toxicity in vitro and in vivo. This directed self-assembly mode can offer a new perspective toward the design of biocompatible antimicrobial nanomedicines for clinical translation.