Traditional treatments for lung cancers can have serious side effects throughout the body, but newly developed, highly targeted treatments could reduce damage, according to Penn State researchers. A team led by Dan Hayes, biomedical engineering department head and Dorothy Foehr Huck and J. Lloyd Huck Chair in Nanotherapeutics and Regenerative Medicine at Penn State, developed a method that could lead to one such treatment with magnetic nanoparticles that can release a therapeutic payload when stimulated using a magnetic field.  Published in Biomedical Engineering Advances, their method enabled nanoparticles to deliver microRNA — molecules that help cells control the kinds and amounts of proteins they make — directly to lung cancer cells in a laboratory model.  

“The goal was to create a platform — this nanoparticle — that could carry microRNA, make it circulate through the body for a long period of time without degrading, but then also give you control over where it's activated,” said Hayes, who is also affiliated with the Materials Research Institute. “MicroRNAs are a potentially very powerful therapeutic, but they're very difficult to get to tissues, and they have a lot of side effects. Our approach addresses the two issues: delivery in the tissue, and its potential side effects and toxicity, because it's only active where we tell it to be active.” 

In the future, Hayes said, the technique could potentially allow a doctor to administer the nanoparticles intravenously and then expose the tumor to an alternating magnetic field radiofrequency (AMF-RF) from outside the body. This would trigger the nanoparticles flowing through the area to heat up slightly and release their therapeutic payload precisely where it is needed.  “It’s a really technical problem that we’re solving,” Hayes said. “These very short chain RNAs that we’re looking at generally are promiscuous; they interact all over the body. So, we can't just deliver them and have them go everywhere, or they'd be very toxic. They're powerful, so we want to get control of where they are active, only in the targeted area of the cancer.” 

In this case, the researchers connected the nanoparticles to a synthetic version of a microRNA called miR-148b, which has been shown to have tumor suppressing activity. Using a heat-sensitive chemical bond called a Diels-Alder cycloadduct, they joined the particles and microRNA, so that the bond would disintegrate and release the microRNA when heated using AMF-RF.  Upon testing their nanoparticles in human lung cancer cells, the research team found the particles successfully entered the cells and released their microRNA payload when exposed to AMF-RF. One day later, a significant number of cells had died in the group that received the nanoparticle/ AMF-RF treatment compared with groups that received nanoparticles with no payload or fully loaded nanoparticles but no AMF-RF. The results demonstrated that the technique has significant promise and could pave the way for more advanced studies, according to the researchers. 

The Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program, the National Institute of Dental and Craniofacial Research of the National Institutes of Health and the National Science Foundation supported this work.  

The other authors on the paper are Julien H. Arrizabalaga, Jonathan S Casey and Yiming Liu, all with the Penn State Department of Biomedical Engineering in the College of Engineering; and Jeffrey C. Becca and Lasse Jensen, both of the Penn State Department of Chemistry in the Eberly College of Science.