Enzyme‐Triggered Transforming of Assembly Peptide‐Modified Magnetic Resonance‐Tuned Probe for Highly Sensitive Imaging of Bacterial Infection In Vivo

Abstract Confirming bacterial infection at an early stage and distinguishing between sterile inflammation and bacterial infection is still highly needed for efficient treatment. Here, in situ highly sensitive magnetic resonance imaging (MRI) bacterial infection in vivo based on a peptide‐modified magnetic resonance tuning (MRET) probe (MPD‐1) that responds to matrix metallopeptidase 2 (MMP‐2) highly expressed in bacteria‐infected microenvironments is achieved. MPD‐1 is an assembly of magnetic nanoparticle (MNP) bearing with gadolinium ion (Gd 3+ ) modified MMP‐2‐cleavable self‐assembled peptide (P 1 ) and bacteria‐targeting peptide (P), and it shows T 2 ‐weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd 3+ . Once MPD‐1 accumulates at the bacterially infected site, P 1 included in MPD‐1 is cleaved explicitly by MMP‐2, which triggers the T 2 contrast agent of MPD‐1 to disassemble into the monomer of MNP, leading the recovery of T 1 ‐weighted signal. Simultaneously, Gd 3+ detaches from MNP, further enhancing the T 1 ‐weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 10 4 CFU) at the myositis site and accurate differentiation between sterile inflammation and bacterial infection based on the proposed MPD‐1 probe suggests that this novel probe would be a promising candidate for efficiently detecting bacterial infection in vivo.