Thermally Triggered, Cell-Specific Enzymatic Glyco-Editing: In Situ Regulation of Lectin Recognition and Immune Response on Target Cells

In situ glyco-editing on the cell surface can endow cellular glycoforms with new structures and properties; however, the lack of cell specificity and dependence on cells’ endogenous functions plague the revelation of cellular glycan recognition properties and hamper the application of glyco-editing in complicated authentic biosystems. Herein, we develop a thermally triggered, cell-specific glyco-editing method for regulation of lectin recognition on target live cells in both single- and cocultured settings. The method relies on the aptamer-mediated anchoring of microgel-encapsulated neuraminidase on target cells and subsequent thermally triggered enzyme release for localized sialic acid (Sia) trimming. This temperature-based enzyme accessibility modulation strategy exempts genetic or metabolic engineering operations and, thus for the first time, enables tumor-specific desialylation on complicated tissue slices. The proposed method also provides an unprecedented opportunity to potentiate the innate immune response of natural killer cells toward target tumor cells through thermally triggered cell-specific desialylation, which paves the way for in vivo glycoimmune-checkpoint-targeted cancer therapeutic intervention.