Long-term antibacterial activity of guanidinium carbon dots without detectable resistance for the effective treatment of pneumonia caused by Gram-negative bacteria

The development of nanomedicine for the treatment of infection caused by resistant bacteria, especially Gram-negative bacteria, is still in the bottleneck. The long-term antibacterial activity and the low induced resistance risk need improvement. Herein, guanidinium-based carbon dots (G-CDs) were prepared from citric acid, dimethyldiallylammonium chloride, and polyhexamethyleneguanidine through melting strategy. The antibacterial properties of G-CDs against Gram-negative and resistant bacteria were investigated. G-CDs exhibit strong and long-term antibacterial activity, as well as antibiofilm activity, with less potential for inducing bacterial resistance. The antibacterial mechanism of G-CDs of the adsorption action and killing effect was elucidated, which was different from the mechanism of antibiotics. Moreover, derived from the interacting mode of nanomaterials and ssDNA, the enhanced ability of G-CDs against Gram-negative bacteria was studied based on the found interaction of G-CDs and lipopolysaccharide (LPS) for the understanding of the mode for the absorption of G-CDs on the cell wall of Gram-negative bacteria. The multimode interactions of van der Waals force, electrostatic adsorption and hydrogen bonding were clarified. Furthermore, G-CDs had excellent in vivo safety and in vivo therapeutic effects in E. coli-infected pneumonia through an intravenous approach. This study provides a hopeful strategy for developing antibacterial drugs from understanding the interacting mode of the drug and the cell wall of bacteria.