The recently discovered method (A novel ‘raspberry-type’ nanoparticle for precise drug delivery), reported in the journal Nanoscale, offers a cheap way to improve the effectiveness of existing drugs.
“If you take sand and heat it at 500 degrees Celsius, nothing changes,” Bradley Smith, Professor Emil T. Hofman professor of science at the University of Notre Dame. So Smith, who is also the director of Notre Dame’s Integrated Imaging Facility, was perplexed when Canjia Zhai and Cassandra Shaffer, two doctoral students from the Department of Chemistry and Biochemistry who worked in his lab, discovered that they had changed the structure of silica particles. – the main part of the sand – at 80 degrees Celsius, a temperature similar to a cup of coffee.
The discovery was made by accident. Those things are very small – one thousandth the diameter of a human hair. But like their larger counterparts called “silica gel” in the package put on new clothes, these particles are disgusting and can hold chemicals. In this case, the chemical is a blue dye used to detect tumors in mice.
The new dye, developed in Smith’s lab, took a long time to penetrate the narrow space of the particles. So, to make the molecules move faster, Shaffer and Zhai heated the mixture under the head and left it overnight. When they returned the next day, they saw that the particles had turned blue.
To confirm that the dye was fully absorbed, Shaffer and Zhai called on Tatyana Orlova and Maksym Zhukovskyi, microscopy experts at the Notre Dame Integrated Imaging Facility.
Orlova and Zhukovskyi produced high-resolution electron microscopy images that showed that not only was the color applied, but the silica particles themselves had changed shape. The first ones are isolated holes with small spots like orange peel. The new structures are spherical, made up of small, pigmented globules. They also have a small hole where the main hole inside is exposed. Everything looks like a raspberry with holes.
After the surprise of the first discovery, there are many useful questions. What other chemicals could the researchers find in the fruit-like material? But, more importantly, will these chemicals continue to work even when their surroundings change their shape?
PhD student Jordan Chasteen took up these questions by replicating the process using anti-cancer drugs. After many tests, he confirmed that the anti-cancer drug embedded in the material still works and can kill cancer cells.
This research provides new tools to make existing drugs more effective, Smith said.
“What we have now is a way to analyze the entire amine-containing drug system, and by following the simple process we discovered, we can create new versions of existing drugs that may be more effective or have unwanted side effects,” he said.
Smith and his students discovered that subtle changes in the loading process allowed them to vary the weight of the particles, providing many new options for manipulating the material to release drugs at different speeds. The unique nature of the new material may also allow it to be used in more than one way – for example, the medicine on the top layer and the egg inside the “raspberry” – to improve the researchers’ ability to see how how the drugs are released.
In addition, the new particle, Smith said, also sheds light on a biological phenomenon known as biomineralization.
“We found that drugs containing amines have certain chemical properties that speed up the process of breaking down and repairing silica, and we believe that this is similar to what happens in nature,” he said. Smith cited as examples diatoms, a type of small plankton, with their fragile glassy shells made of silica.
“These bacteria have a mechanism that allows them to take up sand and fix it in their shell,” he said. “They do this clearly at low temperatures using organic matter. What we discovered may be part of the chemistry behind this process.
As Smith and his lab continue to innovate, they draw inspiration from natural discoveries in the lab. “The big lesson here,” he said, “is that we can find out in the lab how natural processes work, and then we can use that knowledge to model those processes to create new things.”
