New research by the labs of Rice University chemists Stephan Link and Christy Landes has revealed that a protein from cow blood has the remarkable capacity to keep gold nanoparticles from clumping in a solution. The discovery could lead to improved biomedical applications and contribute to projects that use nanoparticles in harsh environments, according to a Rice release.
A paper entitled “Adsorption of a Protein Monolayer via Hydrophobic Interactions Prevents Nanoparticle Aggregation under Harsh Environmental Conditions” published by the American Chemical Society journal ACS Sustainable Chemistry and Engineering, co-authored by Drs. Link and Landes with Rice colleagues Sergio Dominguez-Medina, Jan Blankenburg, and Jana Olson, explains that Bovine serum albumin (BSA) forms a protein “corona” around gold nanoparticles that keeps them from aggregating, particularly in high-salt environments like seawater.
In the ACS Sustainable Chemistry and Engineering article, the Rice researchers explain how they explored the mechanism of the albumin “corona” formation, finding that monolayer protein adsorption is most likely ruled by hydrophobic interactions, and note that for many nanotechnology-based biomedical and environmental applications, particle aggregation and sedimentation are undesirable and could substantially increase the risk of toxicological side effects. Consequently the formation of the BSA corona presented provides a low-cost biocompatible strategy for nanoparticle stabilization and transport in highly ionic environments.
Dr. Link’s primary interest is in the plasmonic properties of nanoparticles, while Dr. Landes’ work incorporates protein binding and molecular transport. The BSA research combines their unique talents with those of Sergio Dominguez-Medina, a graduate student in Link’s lab who studied to be a physicist at Monterrey Tech and was drawn to this interdisciplinary project during an undergraduate fellowship at Link’s Rice lab.
“Initially, we wanted to look at nanoparticles in solution with something they would encounter frequently in blood: serum albumin,” Dr. Landes comments in the release. “In our first experiments, Sergio reported the very efficient, reasonably fast and irreversible binding the moment he put nanoparticles into a solution that contained serum albumin.”
“It turned out the salt is actually driving this binding,” adds Mr. Dominguez-Medina. Without BSA, gold nanoparticles in a salty solution quickly aggregate and fall to the bottom. “That by itself is undesirable for biomedical or industrial applications, because it could lead to toxicity issues,” he notes. “The nanoparticles get more hydrophobic because in the presence of salts, the excess charges on the surface (which discourage clumping) are actually removed.” But if BSA is present, the proteins are drawn to the nanoparticles faster than the particles are drawn to each other. “Once the protein is bound, it gives a super protection against any type of salt-induced aggregation. We think this could be used for the stabilization of nanoparticles in environments where, right now, it hasn’t been achieved,” Dominguez-Medina explains.
The Rice release adds that the capacity of gold nanoparticles to absorb and redirect light is key to several breakthrough technologies being developed at Rice and elsewhere, notably a nanoparticle-based cancer treatment now in human testing that was developed by Professor Naomi Halas and former Rice colleague Jennifer West, and Prof. Halas’ project to convert solar energy directly into steam for sanitation and water purification.
“The only way nanoparticles exhibit their really nice optical properties in very specific optical frequencies is if they’re separated,” Dr, Landes notes, explaining that because pure gold nanoparticles are so hydrophobic, they naturally clump together in a solution unless chemically treated.
“A lot of industrial effort goes into keeping stuff off of surfaces, like contact lenses and ship hulls,” says Dr. Landes. “That involves chemically altering the surfaces to prevent unwanted adsorption, or in the case of nanoparticles, unwanted aggregation.”
Protecting the surface is costly, Dr. Link adds. “But we found we could take nanoparticles prepared in the cheapest way, with a sodium citrate coating that stabilizes the particles by electrostatic repulsion, and add BSA, which coats the particles and makes them really stable.”
Albumin is the most common protein in blood, and the bovine version shares 98 percent of its amino acid sequence with human serum albumin. “One of its main purposes, biologically, is to take things that aren’t water-soluble, bind to them and make them soluble,” says Dr. Landes. “When you combine it with gold nanoparticles, BSA trades places with the cheap citrate, which isn’t a good protective layer, to form the monolayer corona, which is very strong and protective….One of the problems with desalination applications and, similarly, with fuel cells, is that saline or acidic conditions are very corrosive. That’s why you have to use platinum electrodes in fuel cells – not because they’re better than cheaper materials at catalysis, but because they don’t corrode in a harsh environment.” Dr. Landes sees promise for BSA-treated gold nanoparticles in both applications.
The researchers are now looking at how well gold nanoparticles retain their albumin corona with repeated use. “Gold is expensive,” Dr. Landes notes, “But the beauty of it is that if you can reuse it, it only costs you once.”
The Rice team also want to use spectroscopy to see how the binding mechanism works in real time, Dr. Link said. “We want to study what’s happening at the interface of nanoparticles and biologically relevant media” that may eventually include DNA, RNA and drugs for delivery to cells, he said.
Dr. Link plans to see how BSA can be used in combination with gold nanorods. Because nanorods’ plasmonic properties can be tuned, “we can get them into the biological window, which is near-infrared light,” he notes. Near-IR from lasers is used to activate, by heating, Halas’ and West’s cancer-killing nanoshells. Nanorods may also offer ways to combine BSA and other useful proteins by coating the tips and sides separately.
Other co-authors of the ACS article are Jan Blankenburg, an exchange student at Rice from the University of Mainz in Germany, and Jana Olson, a graduate student and National Science Foundation (NSF) fellow in Link’s lab. Drs. Landes and Link are both assistant professors of chemistry and electrical and computer engineering. Dr. Halas is the Stanley C. Moore Professor in Electrical and Computer Engineering and a professor of biomedical engineering, chemistry, and physics and astronomy. She also is founding director of the Laboratory for Nanophotonics and director of the Rice Quantum Institute.
The Robert A. Welch Foundation, the Cancer Prevention and Research Institute of Texas, the Army Research Office, the NSF and National Institutes of Health supported the research.