This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Sugars, or glycans, play a crucial role in biology—from cell signaling and recognition to interactions with pathogens. Changes in glycosylation are also associated with diseases including cancer.
But studying glycans poses a major challenge: because many glycans are highly water-soluble, or hydrophilic, they cannot easily cross the cell membrane and must be modified with a hydrophobic moiety—a water-repelling chemical group—and prepared and delivered using potentially harmful solvents. Professor Matthew Gibson and his team have demonstrated a new approach using a small superchaotropic nanostructure made of boron to transport these molecules directly into mammalian cells, crucially removing the need for cytotoxic organic solvents such as dimethyl sulfoxide (DMSO). The paper is published in the journal Angewandte Chemie International Edition.
One widely used technique for studying glycans is metabolic oligosaccharide engineering, in which modified sugars carrying a chemical 'handle' are introduced into cells. These sugars, specifically designed to be tracked and followed through the cell, allow researchers to investigate their biological functions. But because these sugars are hydrophilic (water-loving), the hydrophobic cell membrane prevents them from passing through.
To combat this, the research team used the new boron delivery method to introduce unnatural sugars into the cell, where they were metabolized and used to "edit" the cell surface. The "handle" from the modified glycan, now on the cell surface, can potentially be used to reprogram cells or add new functions. "Glycans (sugars) are crucial molecules for the study of health and disease, but also biorefining and biomanufacturing.
We typically accept that we need to chemically alter sugars to get them inside the cells to do their function. This work shows a fairly straightforward method to deliver sugars directly into the cells, and of real importance for us, it eliminates the need for organic solvents," said Gibson, chair in sustainable biomaterials. The researchers also used the technique to investigate recently discovered glycoRNA—RNA molecules associated with glycans that have only recently been discovered.
By removing some of the practical barriers associated with intracellular glycan delivery, the researchers believe the approach could provide new opportunities across glycobiology and cell-surface engineering, as well as related areas including autophagy, cryobiology and infection research. Future research will focus on increasing the amount of glycan that can be transported into cells, with the aim of matching the delivery performance of existing acetylation-based methods. Qiao Tang et al, Intracellular Delivery of Hydrophilic Glycans Using Superchaotropic Clusters, Angewandte Chemie International Edition (2026).
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