Multifunctional Nanoprobes Camouflaged as Bacterial Nutrients for Specific Magnetic Resonance Imaging and Sonodynamic Inactivation of Antibiotic‐Resistant Bacteria within Deep Tissues

Abstract Current magnetic resonance imaging techniques often lack the specificity to distinguish bacterial infections from nonbacterial inflammation. To address this, multifunctional nanoprobes mimicking bacterial nutrients for selective magnetic resonance imaging and sonodynamic inactivation of antibiotic‐resistant bacteria within deep tissues are synthesized. The probes are synthesized via click chemistry by coupling azide‐functionalized maltotriose with alkyne‐modified manganese hematoporphyrin to form self‐assembling nanoparticles. These probes leverage bacterial‐specific ATP‐binding cassette (ABC) sugar transporters for selective uptake. These studies reveal ≈65% probe uptake in Gram‐positive and Gram‐negative bacteria, with negligible uptake (≈1%) in ABC transporter‐deficient mutants. The probes exhibit high relaxivities (up to 11.56 m m ⁻¹ s ⁻¹ longitudinal, 102 m m ⁻¹ s ⁻¹ transverse), enabling detection of methicillin‐resistant Staphylococcus aureus and multidrug‐resistant Escherichia coli at ≈10 ⁴ colony forming unit. In mice, they differentiate bacterial nephritis from nonbacterial inflammation and visualize bacteria in tumors, outperforming gadolinium‐based agents. The hematoporphyrin component provides potent sonodynamic antimicrobial activity, achieving >95% in vivo bacterial elimination. This study offers a precise imaging and therapeutic strategy for deep‐tissue bacterial infections.