MRSA‐Triggered Disassembly of an Immune‐Recruiting NIR Probe for Bacterial Imaging and Clearance

ABSTRACT

Methicillin‐resistant Staphylococcus aureus (MRSA) infections remain a major clinical challenge due to increasing antimicrobial resistance and limited strategies for precise bacterial recognition and clearance. Here, we report an immune‐recruiting supramolecular amphiphile, Dman‐C11 , that undergoes MRSA‐triggered structural reorganization for activatable bacterial theranostics. Dman‐C11 consists of a hemicyanine near‐infrared (NIR) fluorophore, a D‐mannosamine immune‐recruiting motif, and a hydrophobic C11 chain that promotes bacterial membrane association. The amphiphilic architecture drives spontaneous nanoparticle formation with suppressed fluorescence through aggregation‐caused quenching (ACQ). Upon interaction with the MRSA membrane, nanoparticle disassembly redistributes the probe within the lipid bilayer, producing a 20‐fold fluorescence turn‐on response while simultaneously restoring efficient singlet oxygen generation under 655 nm irradiation. The activated photodynamic process induces ferroptosis‐like bacterial death characterized by extensive lipid peroxidation and oxidative membrane damage. Meanwhile, the D‐mannosamine motif promotes immune‐cell recruitment toward bacterial pathogens, thereby facilitating host‐assisted bacterial clearance. In murine wound infection and bacterial keratitis models, Dman‐C11 achieves approximately 20‐fold reductions in bacterial burden without detectable systemic toxicity. This membrane‐triggered supramolecular disassembly strategy establishes a single‐molecule theranostic approach that links bacterial recognition, activatable imaging, photodynamic antibacterial activity, and immune‐assisted clearance for precise treatment of MRSA infections.