Self-assembly CuO-loaded nanocomposite involving functionalized DNA with dihydromyricetin for water-based efficient and controllable antibacterial action.

Abstract

With the antibiotic crisis intensifies, the defense and treatment of pathogen infections in safe and effective fashion has become a critical issue. Herein, we report a novel and advanced type of sterilization agent designed via the functionalization DNA nanocarriers based on dihydromyricetin and CuO-loaded nanoparticles (DNA/DMY-CuO). Firstly, a pure dihydromyricetin (DMY) isolated from Ampelopsis grossedentata is used as a bridge to the stimulate the construction of DNA cross-linking networks by hydrogen bonding. Subsequently, a 3D spherical CuO-loaded nanocomposite (204.39nm) is customized using the DNA/DMY network as a biological template through a simple coordination-assisted self-assembly method, which exhibits a high dispersibility, water-solubility and physiological stability. The reversible physical interactions in nanocarriers allows the selective separation and automatic release of CuO NPs from DNA/DMY-CuO in neutral and wound exudate environments, thereby extending the survival period of CuO NPs by nearly 24h. Meanwhile, the nanocarriers system relied on the strong binding ability of DMY to the outer membrane of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) achieves controlled drug delivery onto the pathogen wall. The advanced antibacterial action of DNA/DMY-CuO also reflected in membrane destruction, cytoplasmic constituent leakages and ATP synthetic pathway cessation, thereby halting cytosolic metalloregulatory mechanisms and minimizing drug-resistant bacteria. In summary, such multi-functional CuO-loaded nanocomposite provides a water-dispersibility, controllable, low cytotoxicity and long-effective platform to address the ever-growing threats of bacterial infections.