Microwave-Engineered 2D Cu-Metal–Organic Framework Derived Cu-Metal–Organic Nanosheet with Supercritical CO ₂ -Enabled Drug Delivery

A two-dimensional copper-based metal–organic nanosheet (Cu-MON) platform was developed from a layered Cu-MOF possessing sql topology and weak interlayer CH-π interactions, enabling efficient top–down delamination. Ultrasound-assisted liquid-phase exfoliation in acetonitrile produced few-layer Cu-MONs with uniform thicknesses of 3–5 nm and exposed active surfaces, as confirmed by AFM, HRTEM, SAED, and PXRD analyses. The two-dimensional architecture markedly enhanced drug-loading performance. Lansoprazole incorporation into Cu-MON achieved a drug loading efficiency of 86.0 ± 4.0% and a capacity of 46.2% via solvent-assisted loading, which was further improved to 89.1 ± 2.7% using supercritical CO 2 impregnation. Spectroscopic and microscopic analyses confirmed strong host–guest interactions without framework degradation and molecularly dispersed drug confinement. LPZ@Cu-MON showed improved antibacterial activity against Staphylococcus aureus and Escherichia coli, with inhibition zones of 25.6 ± 1.5 mm and 23.6 ± 1.5 mm, respectively, and reduced minimum inhibitory concentrations of 128 and 64 μg/mL, respectively. Notably, LPZ@Cu-MON achieved 66.7–70.8% biofilm inhibition at MIC and retained >50% activity at sub-MIC levels. Growth kinetics, SEM, and CLSM analyses confirmed sustained bactericidal action and depth-wise biofilm disruption.