The recipe is simple. Mix mineral salts containing silver and iron with organic solvents. Heat carefully in the oven for five hours and voilà, a brown powder made up of tiny grains visible only with an electron microscope. Each grain consists of a rectangular block with dimensions on the order of millionths of a millimeter, or nanometers (nm). The recipe for these bricks was developed by a team led by physicists Kleber Pirota and Marcelo Knobel of the University of Campinas (Unicamp), who call them brick-type nanoparticles.
This is the first time that the researchers have manufactured nanoparticles in the form of bricks out of magnetite, the mineral used for refrigerator magnets, with a tiny silver core. “The shape, nanometric size, and inclusion of silver intensify the magnetite’s magnetic properties,” explains Pirota. “Additionally, silver has interesting optical and bactericidal properties.”
The physicists hope that the new nanomaterial will be useful in medicine for its potential bactericidal action and perhaps to improve a new cancer therapy known as magnetic hyperthermia. In an advanced stage of clinical trials in Europe and the United States, magnetic hyperthermia currently uses nanoparticles made solely of magnetite that are injected into the blood to fight some forms of cancer. The magnetite of these nanoparticles is covered in molecules capable of sticking only to the surface of tumor cells. After adhering to the tumor, they are agitated by an oscillating magnetic field. The friction generated by the shaking heats the tumor cells until they die. “Hyperthermia can burn early-stage tumors without harming other cells in the body, unlike chemotherapy and radiotherapy,” says Knobel, explaining that his magnetite nanobricks with silver would be able to vibrate with more intensity than the larger, shapeless nanoparticles made only of magnetite currently used in experimental therapies.
Development of the recipe took the Unicamp physicists almost 10 years, supported by funds from FAPESP and the National Council for Scientific and Technological Development (CNPq). “It was a bit like cooking: first add this, then that, and alter the recipe slowly until you get it right,” says Knobel. “We achieved the result thanks to a lot of experience and a little luck.”
At first, his team used the strategies that nanomaterials researchers normally adopt to manufacture nanoparticles made of a noble metal covered by a magnetic shell. First they made the “cores,” heating a silver salt dissolved in liquid until its ions crystallized into nanoparticles with a diameter of up to 20 nm. The following day, the researchers mixed the silver nanoparticles with salts rich in iron and heated the solution, hoping that thick magnetite shells would grow around the nanoparticles.
The result of the two-step recipe, however, was not nanoparticles of the “shell-core” type. Instead, it was a mixture of “flower-type” nanoparticles, with a silver core surrounded by magnetite “petals.” “The silver core was always exposed, and we were never able to cover it with a magnetite shell,” explains Pirota. “These nanoparticles are interesting for certain applications because silver is bactericidal. But not for hyperthermia, because the core releases silver ions that can damage cells other than tumor cells.”
The physicists noted, however, that the smaller the silver nanoparticles, the greater the number of magnetite petals that grew around them. Chemist Román López-Ruiz and physicist Diogo Muraca, colleagues of Knobel and Pirota at Unicamp, then decided to try “cooking” the silver and iron salts together in order to prevent the silver nanoparticles from growing too large. Thus, López-Ruiz and master’s degree student Maria Eugênia Brollo finally developed the perfect recipe: heat the salt solution for 40 minutes until it reaches 200 degrees Celsius, maintain this temperature for two hours until small silver cores form, heat for another 20 minutes until reaching 260 degrees, and then maintain this temperature for another two hours.
Santiago Figueroa, a physicist at the Brazilian Synchrotron Light Laboratory, confirmed the presence of magnetite surrounding the core using synchrotron light techniques and Muraca obtained images of the particles using an electron microscope at the Nanotechnology Laboratory of the Brazilian Center for Research in Energy and Materials (CNPEM). The nanobricks have a width of 13 nm and a length of 15 nm, with a thickness a little greater than the diameter of the silver sphere inside them (about 4 nm).
Why the recipe works and the reason for the rectangular format of the nanoparticles is still unknown. The researchers suspect that silver nanoparticles under 10 nm in size are no longer good metallic conductors of electricity. Below this size, silver insulates electrical charges on its surface. These charges help to attract magnetite around the core, creating a compact, homogeneous magnetite brick. “We are trying to verify this hypothesis,” says Pirota.
“It’s still early to know if this material will be appropriate for use in magnetic hyperthermia,” notes physicist Andris Bakuzis of the Federal University of Goiás. Bakuzis coordinates a team of 25 researchers in the Central-West of Brazil that uses nanoparticles in pre-clinical tests of new medical therapies, including hyperthermia. “The iron in magnetite is absorbed and reused by the body, but silver is toxic.”
Pirota is aware of the difficulty. “Even with the core fully encased, silver ions can still cross through the magnetite,” he explains. Work by other researchers even suggests that, strangely, the bactericidal effect of a silver nanoparticle totally encased in magnetite is even greater than that of a nanoparticle of silver alone. “If this result is confirmed,” concludes Bakuzis, “these particles could have great bactericidal potential.”
BROLLO, M. E. F. et al. Compact Ag@Fe3O4 core-shell nanoparticles by means of single-step thermal decomposition reaction. Scientific Reports. v. 4, n. 6839.Oct 9, 2014.