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

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.