A Target-And-Activate Magnetic Resonance Imaging Strategy for Precision Imaging of Intratumoral Bacteria and Screening Antibiotics to Suppress Breast Cancer Metastasis

Intratumoral bacteria facilitate tumor metastasis, yet their precise detection remains a challenge, as nanoprobes accumulate nonspecifically and small-molecule probes lack sufficient sensitivity. Here, we report a Target-and-Activate magnetic resonance imaging (MRI) Strategy by designing a peptide probe, BS-FFGd, to specifically visualize low-abundance intratumoral bacteria and guide antimetastatic therapy. This probe requires dual-specificity for activation: targeting lipoteichoic acid on Gram-positive bacteria, then being cleaved by tumor-associated matrix metalloproteinase-2. The design of BS-FFGd ingeniously integrates supramolecular chemistry with imaging mechanisms. Upon dual activation, the probe triggers in situ self-assembly into nanofibers on bacteria, prolonging rotational correlation time and amplifying T1 relaxivity from 9.03 to 16.51 mM–1 s–1 (1.41 T). In murine models, our probe provided highly specific visualization of intratumoral Staphylococcus aureus, outperforming clinical Gd-DTPA and a targeting-only control by ∼4.7-fold and ∼2-fold in ΔCNR, respectively. MRI signal intensity showed a linear correlation with bacterial load (R = 0.96), achieving a detection limit of 6 × 104 CFU. Crucially, BS-FFGd served as a screening platform, successfully identifying moxifloxacin as an effective antibiotic, which suppressed metastatic nodules by ∼3-fold compared to an ineffective antibiotic. This work reports a promising strategy for high-fidelity molecular imaging, linking precise diagnosis to effective antimetastatic therapy.