Tandem Targeting and Dual Aggregation of an AIEgen for Enhanced Near-Infrared Fluorescence Imaging of Tumors.

Near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) are excellent probes for tumor imaging, but there still is space to improve their imaging specificity and sensitivity. In this work, a strategy of tandem targeting and dual aggregation of an AIEgen is proposed to achieve these two purposes. An AIEgen, β-tBu-Ala-Cys(StBu)-Lys(Biotin)-Pra(QMT)-CBT ( Ala-Biotin-QMT ), is designed to tandem target the biotin receptor and leucine aminopeptidase of a cancer cell and thereafter undergo CBT-Cys click reaction-mediated dual aggregations in the cell. Experimental results show that Ala-Biotin-QMT renders 4.8-fold and 7.9-fold higher NIR fluorescence signals over those in the "biotin + LAP inhibitor"-treated control groups in living HepG2 cells and HepG2 tumor-bearing mice, respectively. We anticipate that Ala-Biotin-QMT , which has the tandem targeting and dual aggregation property to simultaneously achieve enhanced tumor enrichment and fluorescence onset, could be applied for accurate cancer diagnosis in the clinic in the future.