Near-infrared light controlled fluorogenic labeling of glycoengineered sialic acids in vivo with upconverting photoclick nanoprobe

Sialic acid serves as an important determinant for profiling cell activities in diverse biological and pathological processes. The precise control of sialic acid labeling to visualize its biological pathways under endogenous conditions is significant but still challenging due to the lack of reliable methods. Herein, we developed an effective strategy to spatiotemporally label thesialic acids with a near-infrared (NIR) light activated upconverting nanoprobe (Tz-UCNP). With this photoclickable nanoprobe and a stable N-alkene-d-mannosamine (Ac4ManNIPFA), metabolically synthesized alkene sialic acids on the cell surface were labeled and imaged in real time through fluorogenic cycloaddition. More importantly, we achieved spatially selective visualization of sialic acids in specific tumor tissues of the mice under NIR light activation in a spatially controlled manner. This in situ controllable labeling strategy thus enables the metabolic labeling of specific sialic acids in complex biological systems.