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.