Oxaborole-Functionalized Sialylated Glycan Probe for High-Fidelity Fluorescence Imaging of Cancer Tissue

Cell surface glycosylation performs a pivotal role in various biological processes, impacting cellular communication, immune response, and disease mechanisms. Glycomes on cell surfaces vary significantly, presenting viable biomarkers for identifying cell types and their states. Thus, the development of fluorescent probes to rapidly detect glycans is of great importance for disease diagnosis and the biomarker-mediated delivery of therapeutic agents. Herein, we introduce an oxaborole-based fluorescent probe (SLY), designed to recognize sialylated glycans on cell surfaces, facilitating cell distinction. This probe demonstrates pronounced selectivity for HepG2 and HT29 cells, which overexpress sialyl Lewis x and sialyl Lewis a, respectively, in contrast to cells that do not overexpress these Lewis antigens. Mechanistic studies revealed that the probe binds to sialic acid present on these Lewis antigens and internalizes into the cell via caveolae-mediated endocytosis, ultimately localizing in the mitochondria. Remarkably, the distinct selectivity of this probe allows for the identification of the cancerous regions within the liver at cellular resolution. Our newly developed probe holds immense potential in distinguishing cell types and advancing cancer diagnostics and fluorescence-guided surgery.