Researchers have demonstrated that microscopic drug delivery containers can be magnetically steered to their targets, advancing the development of precision medicine for treating diseases such as cancer.
A multi-university team led by Jie Feng, a professor of mechanical science and engineering in The Grainger College of Engineering at the University of Illinois Urbana-Champaign, demonstrated that magnetic particles encapsulated in lipid vesicles can be used to steer the vesicles through fluids. This work, published in the Royal Society of Chemistry journal Nanoscale, builds on earlier results showing that lipid vesicles can be engineered to release drugs when illuminated with laser light. The resulting system combining both results is a comprehensive prototype for precision and targeted drug delivery.
"The appeal of lipid vesicles for drug delivery is that their structure is similar to a cell, so they can be made to interact only with particular kinds of cells – a significant advantage for cancer treatment," Feng said. "One of the challenges to realizing such vehicles is knowing how to steer them to the correct site. We have shown how to do this using magnetic fields, solving the last big problem before we begin demonstrations ex vivo."
Feng noted that existing medical technologies such as MRI could be repurposed to steer drug delivery vehicles with their magnetic fields, especially since these fields are designed to penetrate the human body. This can be achieved by encapsulating a superparamagnetic particle within the drug delivery vehicle, so it interacts with the externally controlled magnetic field.
The first step in creating magnetically steerable lipid vesicles was developing a reliable method to encapsulate magnetic particles in the vesicles. Vinit Malik, an Illinois Grainger Engineering graduate student in Feng's laboratory and the study's lead author, used the method of "inverted emulsion," in which magnetic particles are added to a solution of dissolved lipids, leading to lipid droplets forming around the particles.
"It was not obvious what the best way to encapsulate lipid particles would be, so there was a large literature search and some trial and error," Malik said. "We had to determine what the best magnetic particle size is, and then we had to figure out that the inverted emulsion method has the highest yields for encapsulated particles."
Next, the researchers demonstrated that magnetic fields could direct the lipid vesicles. Malik developed a 3D-printable platform to mount the magnets securely on a microscope and to place the vesicles in a solution between the magnets. By observing the resulting motion, the researchers observed how speed varied with the ratio of magnetic particle size to vesicle size. They also confirmed that the vesicles only release their cargo when illuminated with laser light after moving to the end of the microfluidic channel.
While these experiments showed that the lipid vesicles moved as expected in magnetic fields, it was necessary to also understand how the magnetic particle pushes the vesicle from within to understand the behavior of the whole device. The Illinois researchers partnered with investigators at Santa Clara University to computationally study the internal dynamics of the vesicle to predict the motion speed. Using the lattice Boltzmann method, they observed how the magnetic particle drags the whole vesicle when moving through a magnetic field.
"It allowed us to expand on our experiments, since it is otherwise difficult to observe or predict the response of such a vesicle system," Malik said. "It gives us predictive power that will enhance design guidelines and allow us to understand the physical mechanisms governing the motion."
Armed with experimental demonstrations of light-induced drug release and magnetic steering, Feng's laboratory now aims to begin in vitro studies demonstrating that the lipid vesicles can be magnetically steered to specific locations through fluids like human blood.
"Our combined results lay the foundation for a comprehensive precision drug delivery system, and we're ready to explore the potential uses in treatment," Feng said. "We're working towards the next step: using a real drug and performing an in vitro study in a microfluidic system that simulates features of biological environments."
This study's other contributors are Chenghao Xu (Illinois Grainger Engineering); Abdallah Daddi-Moussa-Ider (The Open University); Chih-Tang Liao and On Shun Pak (Santa Clara University); and Yuan-Nan Young (New Jersey Institute of Technology).
The article, "Magnetically driven lipid vesicles for directed motion and light-triggered cargo release," is available online. DOI: 10.1039/d5nr00942a .
Support was provided by the National Science Foundation and the Simons Foundation.
Jie Feng is an Illinois Grainger Engineering assistant professor of mechanical science and engineering in the Department of Mechanical Science and Engineering . He is a research affiliate of the Materials Research Laboratory .
