Lanthanide Core–Satellite Nanoprobes with Dually Activatable Magnetic Resonance and Second Near-Infrared Fluorescence Signals for Perioperative Image-Guided Cancer Surgery

Image-guided surgery plays a critical role in improving the cancer patient prognosis. However, current clinical probes are often single-modal with "always-on" signals, failing to provide complementary and precise guidance across all perioperative phases. To tackle this hurdle, we develop a biomarker-activatable, multimodal nanoprobe - LanCop - based on redox-mediated manganese valence switching for tumor-specific, perioperative image-guided surgery. LanCop comprises a lanthanide nanoparticle (LnNP) core surrounded by high-valence manganese-rich MnO_1.69 satellites, which initially exhibits negligible T₁-weighted magnetic resonance imaging (MRI) contrast and second near-infrared (NIR-II) fluorescence. In the glutathione-rich tumor microenvironment, Mn³⁺/Mn⁴⁺ ions are reduced to free Mn²⁺ ions, effectively generating strong MRI contrast via increased unpaired electrons and enhanced spin relaxation and simultaneously disrupting energy quenching between the core and satellites to restore NIR-II fluorescence. This dual-signal activation enables precise preoperative MRI tumor localization, real-time intraoperative fluorescence-guided tumor resection, and rapid optical biopsy confirmation (within 5 min) in mouse glioma models. Deep-seated tumors are detected in real-time with a high signal-to-background ratio (12.6 ± 0.7), and microtumors as small as ∼0.5 mm × 0.7 mm are precisely excised under NIR-II fluorescence guidance. Notably, it accurately distinguishes human glioma specimens from adjacent normal tissue, demonstrating its potential for histopathological assessment. To our knowledge, LanCop is the first activatable multimodal probe capable of guiding all perioperative phases, offering a promising strategy to enhance surgical precision and improve clinical outcomes in cancer treatment.