Delivery of chiral D-cysteine by pH-responsive mesoporous silica nanoparticles for effective bacterial inhibition

Efficient and highly controllable antibacterial effects, as well as good biocompatibility, are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, mesoporous silica nanomaterials (MSNs) carriers with a particle mean size of 60 nm and pore size of 7.9 nm were prepared, which was followed by loading with D-cysteine (D-Cys) and modified with Polyethyleneimine (PEI) molecules on the outer surface (named as D@MSNs-P). The prepared D@MSNs-P showed a good pH response in the range of 5-7, and the rate of antibacterial agent D-Cys released from nanocarriers was much faster at lower pH (pH 5) than that at higher pH (pH 6-7), which favors the rapid control of the pathogenic bacteria. In a working pH (pH 5), D@MSNs-P exhibited broad-spectrum antibacterial activities against Escherichia coli, Staphylococcus aureus, Salmonella enteritidis, and Listeria monocytogenes with the highest antibacterial efficiency of 99.9%, 99.8%, 98.1%, and 96.2%, respectively, which is much higher than that of pure D-Cys, pure MSNs, D@MSNs, and PEI group. The outstanding antibacterial activity of D@MSNs-P was attributed to the synergistic effect of the unique structure of MSNs and chiral D-Cys molecules. In addition, the prepared D@MSNs-P has no cytotoxicity to HepG2 cells (Human hepatoma cells) at the concentration of 0.4-12.8 mg/mL and even can promote cell proliferation at high concentrations. Our results open a new door for designing the most promising nanomaterials for pH response release and controllable antimicrobial.