Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis

Abstract

We have developed a one-step method to synthesize carbon quantum dots (CQD_PAs) from biogenic polyamines (PAs) as an antibacterial agent for topical treatment of bacterial keratitis (BK). CQDs synthesized by direct pyrolysis of spermidine (Spd) powder through a simple dry heating treatment exhibit a solubility and yield much higher than those from putrescine and spermine. We demonstrate that CQDs obtained from Spds (CQD_Spds) possess effective antibacterial activities against non-multidrug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica serovar Enteritidis bacteria and also against the multidrug-resistant bacteria, methicillin-resistant S. aureus. The minimal inhibitory concentration (MIC) of CQD_Spds is ∼2500-fold lower than that of spermidine alone, demonstrating their strong antibacterial capabilities. Investigation of the possible mechanisms behind the antibacterial activities of the as-synthesized CQD_Spds indicates that the super-cationic CQD_Spds with small size (diameter ca. 6 nm) and highly positive charge (ζ-potential ca. +45 mV) cause severe disruption of the bacterial membrane. In vitro cytotoxicity, hemolysis, hemagglutination, genotoxicity, and oxidative stress and in vivo morphologic and physiologic cornea change evaluations show the good biocompatibility of CQD_Spds. Furthermore, topical ocular administration of CQD_Spds can induce the opening of the tight junction of corneal epithelial cells, thereby leading to great antibacterial treatment of S. aureus-induced BK in rabbits. Our results suggest that CQD_Spds are a promising antibacterial candidate for clinical applications in treating eye-related bacterial infections and even persistent bacteria-induced infections.

Keywords: bacterial keratitis; carbon quantum dots; multidrug-resistant bacteria; spermidine; topical administration.