Ultra-small block M’s lead to big ideas in drug delivery

Ultra-small block M’s lead to big ideas in drug delivery

Three layer block M nanoparticles under electron microscopy. Photo by Sai Pradeep Reddy Kobaku, Tuteja Research Group

University of Michigan researchers have created what might be the world’s smallest three-dimensional (unofficial) “block M’s” using a new nanoparticle manufacturing process. The new technique may also pave the way to medications that can target specific cells, deliver multiple drugs at different times and rates and even allow doctors to steer them to specific locations in the body. They could also offer researchers better ways to test new therapies.


The new production technique involves depositing layers of polymer on a silicon wafer. It produces particles that can be ten or more layers thick to incorporate several courses of drug treatment, metals, plastics or virtually any other material. They can be made in precisely controlled sizes and shapes as small as 25 nanometers across.

 

“The block M’s were just a test,” said Anish Tuteja, an assistant professor of materials science in the College of Engineering and a developer of the process. “This opens up all sorts of opportunities for combining different polymers and molecules in a variety of shapes. And because it’s is simple and low-cost, we can explore new possibilities much more easily than in the past.”

 

Researchers say one of the first applications for the particles is likely to be in chemotherapy, where their ability to incorporate multiple layers could enable drug makers to combine several different chemotherapy drugs and target multiple types of cancer cells with a single treatment. They could also layer in magnetic materials that enable doctors to steer the drugs toward tumors.

Another key trait is the particles’ flexible shape, size and makeup, which may enable doctors and drug makers to optimize medications to more effectively target cancer cells and do less damage to healthy cells.

 

“Different types of cancer have different cell structures, and each type can internalize nanoparticles in a different way,” said Geeta Mehta, an assistant professor of materials science and engineering in the College of Engineering who is working on the project. “We can easily tailor the shape and drug combinations of these new particles to each type of cancer, so that they’re more effective against cancerous cells and less harmful to healthy cells.”

 

While any new treatment is likely five to ten years out, the team hopes to have an early iteration of the medications available for testing within one to two years.

 

The particles’ versatility and relatively simple production process also makes them useful in the lab for testing new treatments, and for gaining a better understanding of exactly how medications interact with cells.

 

“The University of Michigan has an extensive library of new cancer drugs in development, and I think these particles are going to help us understand how to use them most effectively,” Mehta said. “We can easily try new combinations of drugs and different particle shapes, and we can include dyes and other markers to see how they behave inside a cell.”

 

What might be the world's smallest (unofficial) Michigan logos demonstrate a nano-manufacturing process that could lead to advanced drug delivery systems. University of Michigan engineering researchers developed the new process.

The particles may be useful for other drug delivery applications as well, including inhalable vaccines and time-release prescription drugs that could be taken far less frequently than current medications.

 

While researchers have successfully created multi-layered nanoparticles in the past, these particles are the first to combine that capability with precise control over the particles’ shape, size and composition.

 

The research team began the production process with a silicon wafer that has a liquid-repellent coating. They used ultraviolet light to etch away the coating in the shape of the final particles. Finally, they dipped the etched wafer into a liquid containing polymer dissolved in a solvent. The liquid settled only on the etched areas, and when the solvent evaporated, the polymer remained, leaving precisely shaped nanoparticles. To get multiple layers, researchers simply dipped the wafer again and again, forming a new layer each time.

 

Tuteja said current methods for manufacturing multi-layered nanoparticles are more complex than the new approach. Most can only produce spherical particles, and controlling particle size is difficult. He said the team is in the process of developing automated manufacturing methods that will eventually produce larger numbers of particles with greater efficiency. The process could potentially be used to manufacture particles for a variety of applications including computer displays, diagnostic sensors and even microscopic motors.


“I think one day, we’ll have programmable machines that can be quickly reconfigured to manufacture any type of particle,” said Macromolecular Science and Engineering graduate research assistant Sai Pradeep Reddy Kobaku, who is working on larger-scale production methods for the particles. “We’re also searching for partner companies who want to participate in the commercialization process.”


A paper on the technique, titled “Wettability Engendered Templated Self-Assembly (WETS) for Fabricating Multiphasic Particles,” will publish in the Feb. 25 issue of ACS Applied Materials & Interfaces magazine. Research was supported by the National Science Foundation and the Office of Naval Research.