Afterglow Resonance Energy Transfer‐Induced Near‐Infrared Afterglow Imaging for Surgical Navigation of Microtumors

ABSTRACT Accurate intraoperative identification and complete resection of tumor lesions are essential for effective cancer treatment, especially for microtumors. However, conventional fluorescence imaging is hampered by tissue autofluorescence interference, limited penetration depth, and low signal‐to‐background ratio (SBR), which restrict its utility in surgical navigation. Herein, we report near‐infrared (NIR) afterglow nanoparticles (TA@M1 NPs) for high‐precision image‐guided surgical resection. By engineering afterglow resonance energy transfer, the afterglow emission is red‐shifted to 820–880 nm, enabling clear visualization through deep tissues and substantially enhanced SBR compared to conventional afterglow nanoparticles. In vivo, TA@M1 NPs achieve precise tumor–normal tissue discrimination with a ratio of 41.7. Guided by NIR afterglow imaging, metastatic tumors smaller than 1 mm are accurately identified and resected, with performance comparable to the gold‐standard system. Furthermore, TA@M1 NPs exhibit strong NIR afterglow with penetration depths up to 4 cm under ultrasound excitation, along with markedly enhanced SBR. In vivo, TA@M1 NPs enable precise identification of orthotopic liver tumors. This work establishes an autofluorescence‐free imaging strategy for surgical navigation of microtumors, offering substantial potential for oncologic surgery.