Abstract

Cell-cell interactions (CCIs) play crucial roles in directing diverse biological processes in multicellular organisms, making the high-sensitivity and selectivity characterization of the diverse CCIs in high demand yet still challenging. We herein introduced a bioorthogonal photocatalytic quinone methide decaging-enabled cell-cell interaction labeling strategy (CAT-Cell) for sensitive and spatiotemporally resolved profiling of multitype CCIs. By adapting an optimized quinone methide probe for interacting cell labeling, we demonstrated the excellent capacity of CAT-Cell for capturing CCIs directed by various receptor-ligand pairs (e.g., CD40-CD40L, TCR-pMHC) and further showed its compatibility with tumor-specific targeting systems. Finally, we used CAT-Cell to detect cytotoxic cells (e.g., antigenspecific T cells, Natural Killer cells) in mouse models containing splenocyte mixtures and tumor samples. By leveraging the bioorthogonal photocatalytic decaging chemistry, CAT-Cell offers as a nongenetic, non-invasive and universal toolbox for profiling diverse CCIs under physiological-relevant settings.