MOF-derived nanozymes loaded with botanicals as multifunctional nanoantibiotics for synergistic treatment of intracellular antibiotic-resistant bacterial infection.

Intracellular bacterial infections caused by antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), pose an intractable threat to public health. Intracellular MRSA is extremely difficult to eradicate using traditional antibiotics due to the poor intracellular accumulation and drug resistance. In this work, a novel multifunctional nanoantibiotic (GZNC) was constructed using MOF-derived nanozymes loaded with botanicals for synergistic treatment of intracellular antibiotic-resistant bacterial infection. The nanoantibiotic integrated glycyrrhizinic acid (GA) into ZIF-8-derived nanozymes (ZNC), which achieved controlled release of GA, excellent photothermal effects and enhanced peroxidase-like (POD-like) activity under near-infrared (NIR) light irradiation. The nanoantibiotic showed excellent potential for in vivo and in vitro eradication of intracellular antibiotic-resistant bacteria. With the merits of NIR light-actuated botanicals/photothermal therapy (PTT)/chemodynamic therapy (CDT), the nanoantibiotic could synergistically eradicate intracellular antibiotic-resistant bacteria and alleviate associated infection, providing a promising and biologically safe pathway to address the intracellular antibiotic-resistant bacterial infection.