An Integrated NIR-II Fluorescence-Free Reporter for Multimodal Imaging-Guided Breast-Conserving Surgery

Breast-conserving surgery is the most common treatment method for the treatment of breast tumors. However, achieving precise tumor margin delineation for improving surgical outcomes remains a foremost challenge. Here, we present a second near-infrared (NIR-II) fluorescence-free reporter (NiS₈) that integrates magnetic resonance imaging (MRI)-photoacoustic imaging (PAI)-surface-enhanced resonant Raman scattering imaging. The nickel-containing NiS₈ exhibits intense photon-resonant absorption but is nonemissive, facilitating the development of fluorescence-free trimodal nanoprobes (RPM nanoparticles) with improved Raman/PAI properties and signal correlation. Upon systemic administration of RPM nanoparticles, preoperative MRI first identifies the location, size, and shape of orthotopic breast tumors for surgical planning. Next, intraoperative Raman scanning enables high-accuracy delineation of tumor positive margins for step-by-step tumor removal in NIR-II, while intraoperative PAI simultaneously visualizes deep-seated residual lesions in the surgical cavity. Finally, postoperative Raman imaging allows for validating clean negative margins in the surgical bed, corroborated by histological staining, thus collectively verifying complete tumor resection.