For the first time, this study compared three types of Ag-doped ZIF-8 nanocomposites (AgNPs@ZIF-8(α), AgNPs@ZIF-8(β), and APTES-functionalized AgNPs@ZIF-8(γ)), besides ZIF-8 and APTES@ZIF-8. The composites were characterized in terms of morphology and crystalline structure, encapsulation capacity, capability to keep silver, antibacterial activity against E. coli and S. aureus, and cytotoxicity to human skin fibroblast (HSK) cell line. TEM analysis showed spherical dots of AgNPs (< 10 nm) on the surface or in matrix of ZIF-8 particles, and also their XPS spectra displayed two peaks corresponding to Ag 3d3/2 and Ag 3d5/2. FTIR analysis confirmed a successful chemical interaction between APTES and ZIF-8 in AgNPs@ZIF-8(γ). All of the nanocomposites displayed a combination of microporosity (<2 nm) and mesoporosity (2–50 nm) structures. BET analysis showed a specific surface area of 1718.5 m2/g for ZIF-8, whereas the amine-functionalized particles (i.e., APTES@ZIF-8 and AgNPs@ZIF-8(γ)) showed a decrease of about 1000 m2/g in the surface area and an increase of about 2 times in pore diameter. Different levels of silver were doped into the nanocomposites: AgNPs@ZIF-8(α), 7.04 mg/g; AgNPs@ZIF-8(γ), 27.17 mg/g; and AgNPs@ZIF-8(β), 38.91 mg/g. MTT test on HSK cells revealed IC50 values of 31.4–39 µg/ml for the three Ag-doped ZIF-8 and a higher IC50 (48.2 µg/ml) for ZIF-8. AgNPs@ZIF-8(β) and AgNPs@ZIF-8(γ) displayed MICs of 400 µg/ml and between 400 and 600 µg/ml against both E. coli and S. aureus, and the Ag-doped composites illustrated an Ag-loading content dependency to induce antibacterial activity. Taken together, the findings suggest that AgNPs@ZIF-8 nanocomposites could be introduced as a safer alternative for AgNPs or antibiotics to the health and biomedical industries.
