Self-assembled copper tannic acid nanoparticles: A powerful nano-bactericide by valence shift of copper

Pathogenic bacterial infection remains a public health problem worldwide. Traditional antibacterial strategies pose a marked increase in the emergence of drug-resistant strains in a post-antibiotic era, and the development of new therapeutic modalities remains a challenge. Herein, we developed a one-pot green approach to synthesize the copper ions crosslinked tannic acid nanoparticles (Cu@TA NPs) via mixing copper ions and TA in the weak alkaline aqueous solution at room temperature. The simple synthesis process and mild reaction conditions provide an efficient way to produce Cu@TA NPs on a large-scale, 2 L reaction system in our lab, without changing the nano properties. Meanwhile, Cu@TA NPs can firmly anchor onto the surface of the bacterial membrane, triggering the quick release of copper ions and TA in a local acidic environment. The released TA trigger Cu2+ to transform into Cu+, resulting in membrane disruption, remarkably improving the cellular uptake of Cu@TA NPs. The intracellular GSH further promotes Cu+ increase, significantly enhancing reactive oxygen species generation and cytoplasmic protein leakage of bacterial cells. In this way, Cu@TA NPs at 6.3 μg Cu/mL completely inhibited the growth of Gram-positive and Gram-negative bacteria in vitro, overcoming the drawback of Cu2+ as a bactericide. Besides, Cu@TA NPs have the robust penetration ability to reduce the intracellular bacterial burden and biofilm biomass significantly. Furthermore, mouse skin-infected model results show that Cu@TA NPs greatly avoided the re-infection of the wound, contributed to collagen deposition, and accelerated skin regeneration. The developed Cu@TA NPs reveal unparallel superiority as the safety antibacterial nanoplatforms and open new opportunities to design multi-purpose bacterial theranostics agents.