Nowadays, intracellular bacterial infection caused by antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), poses an intractable threat to public health. Intracellular MRSA is extremely difficult to eradicate by traditional antibiotics due to the poor intracellular accumulation and drug resistance. In this work, a novel multifunctional nanoantibiotic (GZNC) was constructed by 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 a controlled release of GA, excellent photothermal effects and enhanced peroxidase-like (POD-like) activity under the near-infrared (NIR) light irradiation. The nanoantibiotic showed the 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.
