Fluorescence‐guided cytoreductive surgery is one of the most promising approaches for facile elimination of tumors in situ, thereby improving prognosis. Reported herein is a simple strategy to construct a novel chainlike NIR‐II nanoprobe (APP‐Ag2S‐RGD) by self‐assembly of an amphiphilic peptide (APP) into a nanochain with subsequent chemical crosslinking of NIR‐II Ag2S QDs and the tumor‐targeting RGD peptide. This probe exhibits higher capability for cancer cell detection compared with that of RGD‐functionalized Ag2S QDs (Ag2S‐RGD) at the same concentration. Upon intraperitoneal injection, superior tumor‐to‐normal tissue signal ratio is achieved and non‐vascularized tiny tumor metastatic foci as small as about 0.2 mm in diameter could be facilely eliminated under NIR‐II fluorescent imaging guidance. These results clearly indicate the potential of this probe for fluorescence‐guided tumor staging, preoperative diagnosis, and intraoperative navigation.
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