Cells have a preference when it comes to nanoparticle shape: discs beat rods, researchers report.
Understanding how nanoparticle shape affects their transport into cells could help scientists design better drug therapies and reduce side effects.
And while geometry is important, different types of cells have different mechanisms to pull in nanoparticles of different sizes, according to the new study published in the Proceedings of the National Academy of Sciences.
“This research identified some very novel yet fundamental aspects in which cells interact with the shape of nanoparticles,” says Krishnendu Roy, of the biomedical engineering department at Georgia Tech and Emory University.
Roy’s team used a unique approach to make the differently shaped nanoparticles. They adapted an imprinting technology used in the semiconductor industry and rigged it to work with biological molecules. This imprinting technique works like a cookie cutter—but on the nanoscale.
Drugs are mixed with a polymer solution and dispensed on a silicon wafer. Then a shape is imprinted onto the polymer-drug mixture using a quartz template.
The material is then solidified using UV light. Whatever the cookie cutter’s template—triangle, rod, disc—a nanoparticle with that shape is produced.
Control the size and shape
Another key feature of the nanoparticles is that they are negatively charged and are hydrophilic, attributes that make them relevant for clinical use in drug delivery.
“We have exquisite control over the shapes and sizes,” says Roy.
His team then used particles of various shapes and sizes to see how different kinds of cultured mammalian cells would respond to them. The materials and surface charges of the particles were all the same, only the shapes differed.
Roy’s team was not expecting cells to prefer discs over rods. They found that in cell culture, unlike spherical nanoparticles, larger sized discs and rods are taken up more efficiently, a finding that was also unexpected.
When they ran theoretical calculations they found that the energy required by a cell membrane to deform and wrap around a nanoparticle is lower for discs than rods and that gravitational forces and surface properties play a significant role in nanoparticle uptake in cells.
“The reason this has been unexplored is that we did not have the tools to make these precisely shaped nanoparticles,” Roy explains. “Only in the past seven or eight years have there been a few groups that have come up with these tools to make polymer particles of various sizes and shapes, especially in the nanoscale.”
Cells take in nanoparticles through a process called endocytosis, but depending on the shape and cell-type, specific uptake pathways are triggered, the team discovered. Some cells rely on proteins in their membranes called caveolin; others use a different membrane protein, known as clathrin.
Understanding how cells respond to the shapes of nanoparticles is important not just for drug delivery, but also for understanding the toxicity of nanomaterials used in consumer products. Roy’s new work provides another piece to solving this puzzle.
“People are making different nanoscale stuff with various materials without fundamentally understanding their interactions with cells,” Roy says.
Researchers at the University of Texas at Austin collaborated on the work, which was sponsored by the National Science Foundation and the National Institutes of Health.
Source: Georgia Tech