Dopant-Engineered Downshifting Nanoparticles with Dual NIR-II Fluorescence and Magnetic Resonance Imaging for Diagnosis and Image-Guided Surgery of Breast Cancer.

As surgery is the first-line paradigm for many solid tumors, precision in preoperative diagnosis and intraoperative imaging is of significant importance. Dual MRI and NIR-II fluorescence imaging could fulfill precision imaging requirements in treating cancers, because of its deep penetration and real-time high spatiotemporal resolution. Thus, the design of dual MRI/NIR-II fluorescence contrast agents is crucial for the diagnosis and surgery of cancers. Herein, we developed optically transparent NaGdF4 matrix-based downshifting nanoparticles (DSNPs) co-doped with Nd, Yb, and Er as a single nanoplatform for dual NIR-II fluorescence and T1-weighted MRI. Systematic dopant engineering reveals that optimal Nd loading enhances cascade Nd → Yb → Er energy transfer and yields intense NIR-II emission at 1334 and 1521 nm upon 808 nm excitation with a relative quantum yield of 1.55, while the presence of Gd in the optically transparent matrix imparts strong T1 contrast (4.98 s mM). The Pluronic F-127 surface coating confers colloidal stability and biocompatibility. In vitro assays confirm negligible cytotoxicity and efficient cellular uptake. In vivo studies in subcutaneous 4T1 tumor-bearing mice demonstrate robust accumulation, high tumor-to-background contrast in both MRI/NIR-II fluorescence and enable precise NIR-II fluorescence imaging-guided surgery with real-time margin visualization. Therefore, dopant-engineered DSNPs represent a promising dual-modal imaging agent for deep-tissue diagnostic and real-time surgical guidance in precision oncology.