Scientists develop method to deliver sugars directly into cells

Scientists have developed a novel method to deliver hydrophilic sugars directly into mammalian cells, bypassing the need for toxic organic solvents traditionally used in glycan delivery. The breakthrough was achieved by Professor Matthew Gibson and his team at the University of Manchester, who utilized a superchaotropic boron cluster to facilitate the transport of these essential biomolecules. Published in Angewandte Chemie International Edition, the study marks a significant advancement in glycobiology and opens new avenues for cellular research and therapeutic applications. The challenge of delivering hydrophilic glycans into cells has long hindered progress in understanding their roles in health and disease. Glycans, or sugars, are vital for cell signaling, immune response, and pathogen interaction, yet their high water solubility makes them difficult to pass through the hydrophobic cell membrane. Traditional methods require modifying glycans with hydrophobic groups and using organic solvents like dimethyl sulfoxide (DMSO), which can be harmful to cells and limit experimental accuracy. Gibson’s team addressed this issue by employing a superchaotropic boron cluster known as B₁₂Br₁₂²⁻. This nanostructure enables the direct transport of hydrophilic glycans across the cell membrane without the need for chemical modification or toxic solvents. Once inside the cell, the sugars are processed and incorporated into glycoproteins, glycocalyx, and even newly identified glycoRNA molecules. This capability allows researchers to track and manipulate glycan structures more effectively, offering potential applications in reprogramming cell surfaces and enhancing cellular functionality. The method was tested using metabolic oligosaccharide engineering, a technique where modified sugars with specific "handles" are introduced into cells to study their biological behavior. By applying the boron cluster delivery system, the team successfully introduced unnatural sugars into cells, where they were metabolized and integrated into cellular components. This process enabled the creation of customizable cell surfaces, which could be used to enhance or modify cellular functions for biomedical purposes. In addition to advancing glycobiology, the technique holds promise for fields such as autophagy, cryobiology, and infection research. The ability to deliver glycans without altering their structure or introducing harmful chemicals could lead to safer and more efficient methods for studying and manipulating cellular processes. Researchers anticipate that future studies will focus on optimizing the delivery capacity of the method to match or exceed current acetylation-based techniques. The study was conducted by Qiao Tang and colleagues, with contributions from Professor Gibson and his laboratory. The findings highlight a shift toward more sustainable and less invasive approaches in cellular research, aligning with broader efforts in green chemistry and biocompatible materials. As the field continues to evolve, the implications of this discovery extend beyond academic inquiry, influencing drug development, biotechnology, and personalized medicine.