3/20/2025 Ben Libman
Andrew Smith's lab has developed a novel one-step method to synthesize water-soluble nanocrystals by using alkoxy ligands, overcoming the instability and environmental waste issues of traditional oil-based synthesis. This breakthrough technique produces nanocrystals that are remarkably stable and uniformly dispersed in water, making them more suitable for biomedical applications. The method significantly reduces hazardous byproducts and is easier to scale, paving the way for widespread use in fields such as drug delivery and medical testing. Smith’s innovation is poised to become a foundational technology for future advancements in both medicine and materials science.
Written by Ben Libman
From medical imaging to solar panels, many technologies of the future rely on nanocrystals. Nanocrystals are tiny particles of material, often only a few nanometers (one billionth of a meter) across. Their microscopic size gives them unique properties, such as the way they interact with light, conduct electricity, or react with chemicals. Some of their numerous applications include drug delivery, medical testing (such as tests for COVID-19), and even everyday products like sunscreen.
However, the traditional way in which these crystals are manufactured has a problem; it leaves them unstable in water. Most nanocrystals are synthesized in oils, which naturally separates from water- picture oil and vinegar in salad dressing. This makes them unsuitable for biological applications, as water is a primary component of life. The main way to overcome this was by replacing the oily molecules coating the nanocrystals with ones more compatible with water, but this challenging two-step process was difficult to scale and severely limited the use of nanocrystals in biomedical applications. Furthermore, this process produces a lot of chemical waste that can be damaging to the environment.
This was the problem Donald Biggar Willett Faculty Fellow and bioengineering professor Andrew Smith set out to solve. His lab developed a novel technique to generate nanocrystals that are hydrophilic in a single step, outlined in a paper recently published in Nature Synthesis. The key is the substance coating the nanocrystal, known as a ligand. Traditional synthesis methods used hydrocarbon ligands, which are hydrophobic. Professor Smith’s lab has pioneered a method in using alkoxy ligands, which can disperse evenly in water. Smith explains: “Traditional hydrocarbon ligands mainly contain carbon and hydrogen atoms, which together make a molecule ‘nonpolar’ and hydrophobic. Alkoxy ligands contain oxygen atoms interspersed throughout the molecule. Oxygen bonds with carbon in the molecule are called ‘polar,’ which makes them interact strongly with water through hydrogen bonds. This makes nanocrystals synthesized using alkoxy ligands compatible with water, and therefore, with biology.”
But water solubility isn’t the only advantage of this new technique. The hydrocarbon ligands and solvents used in the old method generate a lot of waste, often contaminated with heavy metals. This new method eliminates hazardous byproducts, producing instead biodegradable byproducts that can be decomposed and used by microorganisms. This can dramatically reduce waste and environmental harm. These nanocrystals are also remarkably stable- whereas the previous crystals might only be functional for a few days, these new crystals can last for months. The previous method also lost a lot of crystals in the process, which would clump together and be unusable. Smith’s crystals do not have this issue, and appear perfectly uniform in water. These advantages make the production of water-soluble nanocrystals easier to scale, meaning large numbers of these crystals can be more reliably manufactured.
Professor Smith wants his discovery to help other researchers. “We are making these materials available for other research labs to test and use, but they are also much easier to synthesize in a standard chemistry lab than prior methods,” said Smith. “I hope that these can be widely used by researchers who want reproducible nanomaterials for use in biomedicine.” Smith collaborated with the Andre Schleife group in Material Science and Engineering at the University of Illinois Urbana-Champaign to help understand the mechanism that makes these nanocrystals so stable.
This new technology is in early days, and of course there’s still progress to be made. But the potential of these new nanocrystals is massive. They may become a pillar that countless other technologies rely on. In the near future you may take medicine, a blood test, or buy a product that uses Smith’s crystals. This research is another example of bioengineering at Illinois shaping the future.
The full paper is available online here.
Andrew Smith is a Donald Biggar Willett Faculty Fellow. He is a Professor of Bioengineering, Medicine, and Technology Entrepreneurship at The Grainger College of Engineering, University of Illinois Urbana-Champaign and Carle Illinois College of Medicine. He is a Research Theme Faculty at the Omics Nanotechnology for Cancer Precision Medicine (ONC-PM) and Carl R. Woese Institute for Genomic Biology. He is also a Resident Faculty at the Micro and Nanotechnology Laboratory. Smith is an Affiliate Faculty in the Department of Materials Science and Engineering.