A biomimetic Trojan horse nanozyme enables cascade-activated eradication of biofilm and intracellular MRSA

Deep pulmonary infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are difficult to eradicate due to the combined protection of biofilms and intracellular bacterial reservoirs. Here, we report a biomimetic “Trojan Horse” nanozyme platform (HA@MSN-Cip-BM, MSM) that integrates infection-responsive drug delivery, bacterial targeting, and catalytic antibacterial activity into a single cascade-activated system. MSM is constructed by encapsulating ciprofloxacin (Cip) within aminated mesoporous silica (MSN) nanoparticles, sealing the pores with 3-aminophenylboronic-acid-modified molybdenum sulfide quantum dots (BM), and coating the surface with hyaluronic acid (HA) for cellular uptake. Upon exposure to the acidic infectious microenvironment, MSM undergoes an acid-responsive activation process characterized by enhanced ciprofloxacin release, increased accessibility of boronic-acid moieties for bacterial interaction, and ROS-associated antibacterial activity. This spatially confined activation enhances bactericidal efficacy against both biofilm-associated and intracellular MRSA. Mechanistic and transcriptomic analyses, together with evaluation in a chronic pneumonia model, demonstrate effective bacterial clearance, reduced lung inflammation, and good biocompatibility. This work establishes a cascade-responsive nanozyme design paradigm for treating drug-resistant deep lung infections.