Self-Assembled Nanoparticles of Natural Phytochemicals (Berberine and 3,4,5-Methoxycinnamic Acid) Originated from Traditional Chinese Medicine for Inhibiting Multidrug-Resistant Staphylococcus aureus

In the field of antibacterial, nanomaterials are favored by researchers because of their unique advantages. Medicinal plants, especially traditional Chinese medicine, are considered to be an important source of new chemicals with potential therapeutic effects, as well as an important source for the discovery of new antibiotics. MRSA is endangering people's lives as a kind of multidrug-resistant Staphylococcus aureus, which is resistant to tetracycline, amoxicillin, norfloxacin and other first-line antibiotics. It is a hotspot to find good anti-drug-resistant bacteriae, nature-originated nanomaterials with good biocompatibility.We reported the formation of phytochemical nanoparticles (NPs) by the self-assembly of berberine (BBR) and 3,4,5-methoxycinnamic acid (3,4,5-TCA) from Chinese herb medicine, which had good antibacterial activity against MRSA.We found that NPs had good antibacterial activity against MRSA; especially, its antibacterial activity was better than first-line amoxicillin, norfloxacin and its self-assembling precursors on MRSA. When the concentration reached 0.1 μmol/mL, the inhibition rate of NPs reached 94.62%, which was higher than that of BBR and the other two antibiotics (p < 0.001). It was observed by Field-Emission Scanning Electron Microscopy (FESEM) that NPs could directly adhere to the bacterial surface, which might be an important aspect of the antibacterial activity of NPs. Meanwhile, we further analyzed that the self-assembly was formed by hydrogen bonds and π-π stacking through Ultraviolet-Visible (UV-vis), Fourier Transform Infrared Spectroscopy (FTIR), hydrogen Nuclear Magnetic Spectrum (1H NMR), and powder X-ray Diffraction (pXRD). NPs' morphology was observed by FESEM and TEM. The particle size and surface charge were characterized by Dynamic Light Scattering (DLS); and the surface charge was -31.6 mv, which proved that the synthesized NPs were stable.We successfully constructed a naturally self-assembled nanoparticle, originating from traditional Chinese medicine, which had a good antibacterial activity for MRSA. It is a promising way to obtain natural nanoparticles from medicinal plants and apply them to antibacterial therapy.