Micrococcal Nuclease-Activated Theranostic Probe for Specific Imaging and Targeting Photothermal Eradication of Intracellular Staphylococcus aureus in Joints in vivo.

The intracellular survival of Staphylococcus aureus (S. aureus) within immune cells poses a significant clinical challenge, driving recurrent infections and antibiotic resistance in orthopaedic practice. Specific identification and precise eradication of intracellular S. aureus are therefore crucial for effective infection management. However, specific visualization of intracellular S. aureus remains challenging due to interference from extracellular bacteria and low intracellular pathogen abundance in vivo, complicating efforts to eliminate them in situ. Herein, we developed a micrococcal nuclease (MNase)-activatable multifunctional theranostic probe, AuTPC@AB, for specific imaging and targeted photothermal eradication of intracellular S. aureus in joints in vivo. The probe operates through a dynamic three-step process: (1) apoptotic body (AB)-mediated targeting to immune cells; (2) activation by S. aureus-secreted MNase, which triggers near-infrared Cy5.5 fluorescence for specific bacterial visualization; and (3) targeted photothermal ablation by target peptide-modified gold nanorods (AuNRs) under laser irradiation. Administration of the AuTPC@AB probe yielded strong fluorescence signals exclusively in S. aureus-infected joints, achieving the differentiation of intracellular S. aureus infection from other bacterial strains. And the subsequent AuNRs-based photothermal therapy effectively eliminated the targeted bacteria in joints. These findings demonstrated that the selective activation of fluorescence imaging and targeted photothermal ablation of intracellular S. aureus, highlighting the clinical potential of the AuTPC@AB for precise diagnosis and treatment of intracellular S. aureus infections.