Quantum Dots with Phenylboronic Acid Tags for Specific Labeling of Sialic Acids on Living Cells

Abstract

Sialic acids with a nine-carbon backbone are commonly found at the terminal position of the glycans structures on cell membranes. The unique distribution and ubiquitous existence of sialic acid on the cell membrane make them important mediators in various biological and pathological processes. We report a new class of imaging probes based on semiconductor quantum dots with small molecular phenylboronic acid tags for highly specific and efficient labeling of sialic acid on living cells. Our results have shown that the use of these probes enables one-step labeling and continuous tracking of the cell surface sialic acid moieties without any pretreatment of living cells. The one-step procedure with fast binding kinetics and the biocompatibility of these probes make it an ideal noninvasive technology for living cell imaging. We also find that the labeled sialic acids undergo quick internalization shortly after surface binding via endocytosis and eventually distribute in the perinuclear region. This distribution pattern is consistent with the notion that sialylated glycoproteins are populated on cell membranes and recycled through the vesicular exocytotic and endocytic pathways. The superior photostability and brightness of quantum dots enable quantitative analysis of the diffusion dynamics of sialic acids, which has been a significant challenge for glycan imaging.

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“…Duan and colleagues employed carbodiimide chemistry in combination with a phenylboronic acid (PBA)-diol reaction to specifically label living cells with a QD-PBA conjugate. 203 They functionalized the hydrophobic QDs by an amphiphilic copolymer of maleic anhydride and octadecene (PMO) to obtain water-soluble QDs with carboxyl groups, which can react with 3-amino-phenylboronic acid (APBA) via an EDACcatalyzed reaction to form QD-PBA conjugates. The PBAdiol reaction allows for specific labeling of sialic acid by the QDs, and the bright QDs enable quantitative analysis of diffusion dynamics of sialic acids on the membrane.…”

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“…Previous research reported that phenyl-boronic acid (PBA) can form favorable bonds with sialic acid among common carbohydrates on the cell surface at the physiological pH of 7.4 (Otsuka et al, 2003). Recently, Liu et al, proposed the use of PBA-tagged quantum dots to label sialic acid on cell membranes for fluorescence imaging (Liu et al, 2010). Inspired by their work, we adopt DBA, a compound that consists of sialic acid capture moiety (phenyl-boronic) and alkyne functional group in our designed study (Fig.…”