The engineering and understanding of nanoparticle function for nanomedicine is well underway, however, one question that has eluded scientists is how the shape of nanoparticles alters their ability to get into cells. This is of great importance, as the idea is to design therapies for diseases that will improve efficacy of cancer drugs as well as reduce side effects. Additionally, different cell types have different mechanisms to pull in nanoparticles of different sizes and shapes. According to the current study, disc-shaped versus rod-shaped nanoparticles are the preferred shape of mammalian cells under normal culture conditions.
According to Krishnendu Roy, of the Walace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, “This research identified some very novel yet fundamental aspects in which cells interact with the shape of nanoparticles”. Roy, in collaboration with Profs. S. V. Sreenivasan and Li Shi, conducted the current project at the University of Texas at Austin, but remains at Georgia Tech to continue his research there. The current research is available in the journal Proceedings of the National Academy of Sciences online edition (Oct. 7)
Roy and colleagues have been able to alter an imprinting technology used in the semiconductor industry and make it work with biological molecules. Simply put, this system works like a cookie cutter but of course on the nanoscale. For drug administration, a polymer solution is mixed with the drug of interest and dispersed on a silicon wafer. By using a quartz template (cookie cutter) a shape is imprinted onto the drug-polymer mixture such as rod, disc or triangle. The entire system is then solidified using UV light. Interestingly, the nanoparticles have a negative charge along their surface which imparts a hydrophilic character which is extremely useful for clinical/drug applications. Roy notes, “We have exquisite control over the shapes and sizes.”
The idea behind the experiment was to test various shapes of nanoparticles and see how mammalian cells in culture reacted to them. The researchers kept the material and surface charge the same. In other words, only the shapes were varied.
Roy and colleagues were surprised to see that cells preferred discs over rods. The researchers were also surprised to see that larger sized discs and rods are taken up more efficiently than their spherical counterparts. To get a better grasp of what was going on, the researchers ran theoretical calculations on this system and found that energy required by a cell membrane to indent and wrap around a particle is lower for discs than rods and that gravitational forces and surface properties are at play in nanoparticle uptake into cells.
It isn’t just a matter of the nanoparticle shape but rather cell membrane components which vary in different cell types. Cells take in particles through a process known as endocytosis. Depending on cell type, different uptake mechanisms are used. For example, come cells use a protein in their membranes known as caveolin which has one way of working and yet others use clathrin which has a different molecular mechanism.
This information is important not only for clinical applications such as drug delivery but also understanding toxicity of nanomaterials used in consumer products. As Roy points out, “People are making different nanoscale stuff with various materials without fundamentally understanding their interactions with cells”. Roy goes on further to say, “99.9 percent of our work is still to be done, which we want to continue to do here at Tech in collaboration with researchers at UT.”