Nanotech News

September 26, 2005

Optimizing Nanoparticle-Cell Interactions Using Microfluidics

Thanks to the work of chemists and material scientists, cancer researchers have a wide array of nanoparticulate materials to choose from when designing a new nanoscale drug delivery or imaging agent. While variety is good, that cornucopia of choices can leave a researcher at whit’s end when it comes to choosing the right nanoparticle for a particular task.

But thanks to work from the Massachusetts Institute of Technology and Harvard Medical School, researchers now have a new tool that will enable them to rapidly assess how well a given set of nanoparticles interact with a selected type of cell. Such data should enable researchers to better select the optimal nanoparticle for a given application before conducting in vivo experiments.

Writing in the journal Analytical Chemistry, a research team headed by Robert Langer, Ph.D., describes its work designing and building a lab-on-a-chip device in which microfluidic channels are lined with cells. In the model system they detail, the investigators used two different prostate cancer cell lines that differ in the amount of prostate specific membrane antigen (PMSA), a well-known tumor marker, on their cell surfaces. Each type of cell was coated onto the sides of its own microfluidic channel. As a targeting ligand, the researchers used an aptamer, small, synthetic stretches of DNA or RNA that function like much larger protein antibodies, that binds specifically to PMSA.

The researchers prepared polymer nanoparticles in a variety of sizes and loaded each with a fluorescent dye, which served as both a model drug compound and as a means to visualize the particles within the microfluidic device. The researchers divided each type of nanoparticle into two pools and attached the anti-PMSA aptamer to the nanoparticles in one of the two pools. They then flowed the nanoparticles through the microfluidic channels and used a fluorescent microscope to measure how much of each nanoparticulate formulation stuck to each particular type of cell.

The results showed clearly that only those nanoparticles with anti-PMSA aptamer were able to bind to the cells containing the PMSA antigen on their surfaces. The labeled nanoparticles did not bind to the cells that did not express PMSA, and unlabeled nanoparticles did not bind to either cell type. The researchers found that the rate at which they flowed the nanoparticles through the microfluidic channels had a critical effect on nanoparticle-cell binding, with slower-moving streams binding more efficaciously than faster moving ones. So, too, did the size of the particle, with larger particles binding less effectively than smaller particles. The researchers hypothesized that larger particles experience more shear force from the moving fluid than do smaller particles. This finding could be relevant information for applications in which nanoparticles were expected to bind to cells lining blood vessels, as would be the case for nanoparticles designed to target angiogenesis.

This work is detailed in a paper titled, “Microfluidic system for studying the interaction of nanoparticles and microparticles with cells.” An abstract is available through PubMed.
View abstract.