Layer-by-Layer Decorated Nanoscale ZIF-8 with High Curcumin Loading Effectively Inactivates Gram-Negative and Gram-Positive Bacteria.

Abstract

Bacteria-mediated infectious diseases have become a health-care challenge globally since the development of antibiotic resistance. Reactive oxygen species produced by photosensitizers have great potential in fighting bacterial infections, especially against Gram-negative bacteria that are hard to kill by regular methods owing to their formidable defensive membrane structures under the premise of avoiding overuse of antibiotics. In this work, a small molecular photosensitizer, curcumin (CCM), was used as a model and encapsulated into zeolitic imidazolate framework-8 (ZIF-8). Then the ZIF-8 loaded with CCM (CCM@ZIF-8) was decorated with biocompatible polymers hyaluronic acid (HA) and chitosan (CS) by the layer-by-layer self-assembly technique to yeild in an antibacterial CCM@ZIF-8@HA@CS nanoparticle with a high local positive charge density and is capable of binding the surface of bacteria by electrostatic interactions. The CCM drug loading capability of the nanoparticle was found to be as high as 10.89%. Upon exposure to blue light (72 J/cm2) for 10 min, the minimum inhibitory concentration and minimum bactericidal concentration of CCM@ZIF-8@HA@CS against Gram-positive bacteria (G(+)) Staphylococcus aureus (S. aureus) and Gram-negative bacteria (G(-)) Escherichia coli (E. coli) were the same, which were as low as 0.625 and 2.5 μg/mL, respectively, showing highly effective antibacterial activities. After treatment with CCM@ZIF-8@HA@CS under blue-light irradiation, the membranes of S. aureus and E. coli folded and cracked. Importantly, the antibacterial agent showed good biocompatibility in the cytotoxicity test using L929 cells and hemolysis test using rabbit blood cells under blue-light irradiation. Therefore, this CCM@ZIF-8@HA@CS nanocomposite is expected to find application in the treatment of superficial traumatic and refractory chronic infections caused by G(+) and G(-).