Size, shape and charge matter when it comes to nanoparticle drug delivery, new Concordia research shows
A team of Montreal researchers using nanotechnology in order to fight cancer cells is examining how the tiniest differences can affect the efficacy of a nanoparticle’s drug delivery.
In a recent paper published in the American Chemical Society’s journal Applied Bio Materials, researchers from Concordia and McGill look at the mechanism of the nanoparticle’s cell uptake. In other words, what gets the drug delivery vehicle into the cell so it can then release the drug.
“We want to look at how the nanoparticle’s drug gets across the membrane to release the drug at the cell site,” says study co-author John Capobianco, a professor in the Department of Chemistry and Biochemistry and the Concordia University Research Chair in Nanoscience.
The researchers, led by Capobianco’s former PhD student Paola Rojas-Gutierrez, worked on lung cancer cells cultured in a lab. They compared the performances of different nanoparticles and isolated different pathways by which nanoparticles entered into the cells, a process called endocytosis. This, says Capobianco, is one of the few studies that looks at the internalization process.
They also found that size and shape play a role in that process. The most effective penetration occurred when the diamond-shaped nanoparticle was positioned so its apex was perpendicular to the cell’s surface.
Further, the researchers noted that a nanoparticle’s charge played an important role in how it spread throughout the cell after it had been internalized. They were then able to use low-energy light to stimulate the nanoparticle to release a model drug called Nile red.
Fighting cancer at the smallest level
As the name implies, nanoparticles are extremely small. The lab-synthesized particles are usually around 100 nanometres across — one nanometre being one-billionth of a metre. For comparison, a human hair is about 100,000 nanometres across. A water molecule is 0.275 nanometres.
In this system, a light-emitting nanoparticle was engineered to be coated with a light-responsive lipid bilayer. The nanoparticles synthesized in this lab emit light through a complex process known as upconversion. This involves irradiating the nanoparticle with infrared light. The nanoparticle converts the low-energy infrared light into ultraviolet light, exciting the photo-switchable molecules in the lipid bilayer. This disrupts the bilayer and allows the drugs to escape and enter a cell.
The researchers hope that eventually, health practitioners will be able to use infrared light to irradiate a small area of a patient’s body, like a tumour. Because the light would be limited to that area, the cell-killing medicine would only be released in that specific location, making this method far more precise and far less invasive than traditional chemotherapy, where cancer-fighting drugs attack all the cells in the body.
The research done by Capobianco’s team backs this up. As they monitored the spread of the Nile red dye throughout the cells they were experimenting on, they noted that very little escaped the nanoparticle vehicle without light stimulation. The little that was released was the result of biological triggers such as enzyme degradation.
“This particular red dye fluoresces, so we were able to see where the drug goes specifically once it is inside the cell,” he says. “Which part of the cell does it go to? The nucleus, or somewhere else?” By knowing the answers to these questions, progress can be made toward developing more efficient and specific treatments with fewer side effects.
The study was also co-authored by Devesh Bekah and Jan Seuntjens, PhD student and professor, respectively, from the McGill University Health Centre’s Medical Physics Unit, and Christine DeWolf, professor and chair of Concordia’s Department of Chemistry and Biochemistry.
The Natural Sciences and Engineering Research Council (NSERC) supported this research.
Read the cited paper: “Cellular Uptake, Cytotoxicity and Trafficking of Supported Lipid-Bilayer-Coated Lanthanide Upconverting Nanoparticles in Alveolar Lung Cancer Cells.”