Nanoparticles, Made to Order – Inside and Out
A new coating technology developed at the Massachusetts Institute of Technology (MIT), combined with a novel nanoparticle-manufacturing technology developed at the University of North Carolina at Chapel Hill, may offer scientists a way to quickly mass-produce tailored nanoparticles that are specially coated for specific medical applications. Using this new combination of the two existing technologies, scientists can produce very small, uniform particles with customized layers of material that can carry drugs or other molecules to interact with their environment, or even target specific types of cells.
“Creating highly reproducible batches of precisely engineered, coated nanoparticles is important for the safe manufacture of drugs and obtaining regulatory approval,” says Paula Hammond, a member of the MIT-Harvard Center of Cancer Nanotechnology Excellence and co-leader of the team that developed this new process for manufacturing nanoparticles. “Everyone’s excited about nanomedicine’s potential, and there are some systems that are making it out to market, but people are also concerned about how reproducible each batch is. That’s especially critical for applications such as cancer therapies,” Dr. Hammond said.
“Fortunately,” she added, “we have combined two technologies that are at the forefront of addressing these issues and that show great promise for the future of nanomanufacturing.” Hammond and collaborator Joseph DeSimone, who heads the Carolina Center for Cancer Nanotechnology Excellence at the University of North Carolina at Chapel Hill, are the senior authors of a paper describing the technology that was published in the journal Advanced Materials.
Dr. Hammond’s lab has developed various technologies for coating nanoparticle surfaces with alternating layers of drugs, RNA, proteins or other molecules of interest. Those coatings can also be designed to protect nanoparticles from being destroyed by the body’s immune system before reaching their intended targets. For this study, her group used a layer-by-layer spray-based technique, which allows them to apply each thin layer in just a few seconds. While this “LbL” technique has been available for years, and is very efficient for bulk surfaces, it has suffered from many throughput challenges for nanoparticle use.
The MIT team then wedded this spray process with a nanoparticle-manufacturing technology known as the PRINT (Particle Replication In Non-wetting Templates) platform, which was developed in Dr. DeSimone lab. The PRINT platform is a continuous roll-to-roll particle-molding technology that enables the design and mass production of precisely engineered particles of controlled size, shape and chemical composition. To make particles such as the ones used in this study, a mixture of polymers and drug molecules is applied to a large roll of film that consists of a nano-sized mold containing features of the desired shape and size. The mixture fills every feature of the mold and solidifies to create billions of nanoparticles. Particles are removed from the mold using another roll of adhesive film, which can then be sprayed with layers of specialized coatings using Hammond’s novel technology and separated into individual particles, a much more efficient production of LbL nanoparticles than had ever before been achieved.
“The idea was to put these two industrial-scale processes together and create a sophisticated, beautifully coated nanoparticle, in the same way that bakeries glaze your favorite donut on the conveyor belt,” explained Dr. Hammond. This new process promises to yield large quantities of coated nanoparticles while dramatically reducing production time. It also allows for custom design of a wide variety of materials, both in the nanoparticle core and in the coating, for applications including electronics, drug delivery, vaccines, wound healing or imaging.
To demonstrate the potential usefulness of this technique, the researchers created particles coated with hyaluronic acid, which has been shown to target proteins, called CD44 receptors, which are found in high levels on aggressive cancer cells. They found that breast cancer cells grown in the lab engulf particles coated with layers of hyaluronic acid much more efficiently than particles without the coatings or with coatings not containing hyaluronic acid.
This work, which is detailed in a paper titled, “Scalable manufacture of built-to-order nanomedicine: Spray-assisted layer-by-layer functionalization of PRINT nanoparticles,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.