In Situ Self‐Assembled Nanofibers Precisely Target Cancer‐Associated Fibroblasts for Improved Tumor Imaging

Abstract Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide‐based near‐infrared probe that is responsive to fibroblast activation protein‐α (FAP‐α), and specifically forms nanofibers on the surface of cancer‐associated fibroblasts (CAFs) in situ. The assembly/aggregation‐induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5‐fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four‐ and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.