Designing of membrane-active nano-antimicrobials based on cationic copolymer functionalized nanodiamond: Influence of hydrophilic segment on antimicrobial activity and selectivity.

Abstract Designing cationic nano-antimicrobial is a promising solution for combating drug resistant microbes. In this work, hydrophilic cationic copolymer was applied for the surface functionalization of nanodiamonds (NDs) aiming at developing a highly membrane-active nano-antibacterial agent with satisfactory selectivity. As a result, after functionalization, the increased repulsive forces within NDs and interaction with solvent molecular network made the heavily aggregated pristine NDs break down into tiny nanoparticles with particle size ranging from 10 to 100 nm. The improved hydrophilicity and enlarged surface area endowed QND-H 5 and QND-H 10 a powerful bactericidal capability toward both of Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus aureus ( S. aureus ). In the further bactericidal assessment, it was also demonstrated that the formation of hydrogen bonding between the 2-hydroxyethyl methacrylate (HEMA) side chains and lipid head groups of bacterial membrane also contributed to the enhanced bactericidal ability. Field emission scanning electron microscopy analysis confirmed that as-prepared nano-hybrid acted bactericidal ability via physical nature of outer membrane and cytoplasmic membrane-separating destruction mechanism toward E. coli , which may derive from the hydrogen bonding ability, making them more effective toward bacterial. More importantly, it was found that with just 10% of HEMA, QND-H 10 displayed good selectivity toward bacteria over mammalian cells as shown by the high HC 50 values with relatively low MIC values, suggesting the great potential application in medical fields. These results indicate that hydrogen bonding is an important element to achieve the desired high antibacterial activity and selectivity, particularly when cationic nano-antibacterial agents are required for medical application. Graphical abstract The functionalized NDs displayed excellent antibacterial property and selectivity and destroyed the bacterial cell membrane through membrane-separating destruction. Unlabelled Image Highlights • HEMA-containing cationic copolymer functionalized NDs were prepared. • The stability, antibacterial ability and biocompatibility of functionalized NDs were greatly enhanced by hydrophilic HEMA. • The as-prepared NDs displayed a membrane-separating destruction toward E. coli. • Hydrogen bonding is an important element to achieve the desired high antibacterial activity and selectivity. [ABSTRACT FROM AUTHOR]