Smart Nanoparticles

Researchers at the Carolina Center of Cancer Nanotechnology Excellence at the Univ. of North Carolina, Chapel Hill are exploring the role of size, shape and deformability in the in vivo behavior of PRINT (Particle Replication In Non-wetting Templates) particles. In this research, biomimetic hydrogel particles have been fabricated which replicate the size, shape and deformability of red blood cells. The mechanical properties of the particles can be adjusted so that they are capable of extreme deformations, allowing these 6 µm diameter particles to navigate approximately 3 µm splenic sinusoids. Splenic sinusoids filter red blood cells as they age and less able to deform. Researchers hope that avoidance of these clearance organs will lead to extremely long circulating particles which will have utility as contrast agents, drug delivery vectors, and in gas transport. Image courtesy of Joseph M. DeSimone, PhD; Mary E. Napier, PhD; and graduate student Timothy J. Merkel.

The methods for delivering cancer drugs to patients are dangerous, pumping toxic chemotherapy drugs or imaging agents throughout the whole body in hope that they get to the tumor. That is, until now. Nanotechnology brings a certain set of tools that can address the currently unmet need of safe drug delivery and safe imaging agents.

The Carolina Center of Cancer Nanotechnology Excellence, Chapel Hill, N.C., a National Cancer Institute (NCI)-designated center of excellence for nanotechnology in cancer, developed "smart" nanoparticles to help meet the need for a safe drug delivery system. The nanoparticles were developed for cancer therapy and cancer imaging.

"A lot of the unmet needs within cancer therapy and treatment lies in getting the drugs/medication directly to the tumor. Nanomedicine can give doctors targeted therapies, and is becoming increasingly important in cancer detection," says Joseph M. DeSimone, Chancellor’s Eminent Professor of Chemistry, North Carolina Univ., and co-founder of Liquida Technologies.

DeSimone and his team were working on nanotechnology when they developed a new method for making particles using nanotechnology in medicine. They started looking at what problems could be solved with this breakthrough approach called PRINT. Nanomedicine was the choice.

The PRINT, or particle replication in non-wetting templates process, generates "smart" nanoparticles. It acts as a molding technology that allows DeSimone and his team to mold particles on the nano-scale. "We developed a roll-to-roll processing technique that allows for the continuous fabrication of particles that have controlled size, shape, and chemistry," says DeSimone.

Although first developed with a focus on making transistors in the semiconductor industry, the PRINT technology was developed in a breakthrough in DeSimone’s lab.

"We were focusing on patterning technology that is useful for making computer chips, and we realized we could extend it into particles of controlled size or shape," he explains. This development opened the door to nanomedicine in a way that allowed for the creation of a more effective cancer therapy and imaging agent. The reason for this is that the controlled size and shape of the nanoparticles go directly to the tumor or spot where they are needed. "The PRINT technology has bridged two fields which have never been bridged before, and that is semiconductor-like processing and precision with medicine," DeSimone says.

The "smart" nanoparticles created by DeSimone and his team can range from 100% drug to half-drug, half-biocompatible material. Thanks to the PRINT technology, these particles can be made out of any chemistry or composition. These particles are made specifically for inhalation. DeSimone describes the process: "When the particles are inhaled and get to where they belong, the matrix of the particle would dissolve into benign materials, but would leave the chemotherapy agent right there to kill the cancer cells."

DeSimone's team of researchers are currently conducting both basic science and applied science trials with their "smart" nanoparticles. "The basic science trial results allowed us to know that the particle size, shape, and chemistry holds a big role as to where the particles will go into the body. My lab is trying to establish what we call biodistribution maps of where particles will go according to the size, shape, and chemistry," DeSimone states. If DeSimone and his collegues could figure out where all the different sizes and shapes would go, then eventually the team could add any drug they wanted to the nanoparticles. From there, they could direct drug companies to use a specific type of particle to direct a drug to go to a certain tumor in an organ.

"The team is also trying some of these systems in parallel with basic science projects in actual animal models," says DeSimone. The team has already had great success using their "smart" nanoparticles in cells, according to DeSimone. He says, "We know we have beautiful targeting of cells. We can deliver chemotherapy agents into the cell. The "smart" nanoparticles are really great at killing cells, even drug-resistant cells. And, now, we are in the animal model stage."

Not only are these nanoparticles important to drug delivery, but they are also important to cancer imaging. "You have the ability to load a beacon of some type that can be detected by imaging," DeSimone says. Since the nanoparticles go to the right place, "you can load a beacon with magnetic resonance, an MRI contact agent, so you can image," he says. What excites DeSimone more is that these "smart" nanoparticles are paving the way for theranostics, the combination of therapy and diagnostics.

Published in R & D Magazine: Vol. 51, No. 4, August, 2009, p.16.