Medical Device Daily Staff Reporter

For years researchers would constantly hit a proverbial brick wall when it came to safely guiding nanoparticles into cell cultures. Previous formulations, which heavily revolved around magnetically guiding the nanoparticles to the diseased cell, were ripe with complications that ranged from the clotting of blood vessels to the inflammation of a cell tumor — possibly leading to infection.

Getting magnetically-driven nanoparticles into human beings just wasn't an option, and the potential for a new way of delivering gene therapy proved to be extremely elusive.

But a new study from the Children'sHospital of Philadelphia is shedding some extensive light on the compatibility of nanoparticles along with other cells —offering a way for the extremely small particles to benefit blood vessels damaged by arterial disease and to bolster support for nanotechnology applications.

The study will be presented in this month's addition of the FASEB Journal, published by the Federation of American Societies for Experimental Biology (Bethesda Maryland).

"Our study represents an advance in the [nanoparticle arena] because of magnetic targeting," Robert Levy, MD, the William J. Rashkind Endowed Chair in Pediatric Cardiology at the Children's Hospital of Philadelphia told Medical Device Daily .

The materials composing the nanoparticles in this study are biodegradable, so they break down into simpler, non-toxic chemicals that can be carried away in the blood.

Previous researchers had proven that magnetically driven nanoparticles could deliver DNA in cell cultures —but Levy's was the first delivery system that was biodegradable and was safer to use in people.

"The formulation we have doesn't aggregate and is biodegradable," he said. "Previous formulations just weren't safe."

For about a year-and-a-half Levy and researchers from the hospital experimented with injecting iron oxide into the nanoparticles, which carried a surface coating of DNA bound to an organic compound called polyethylenimine (PEI). The PEI protected the DNA from being broken down by enzymes called endonucleases that were present in the cell cultures and which occur normally in the bloodstream.

The DNA was in the form of a plasmid, a circular molecule that carried a gene that coded for a growth-inhibiting protein called adiponectin. By applying a magnetic field, the study team steered the particles into arterial smooth muscle cells. Inside each cell, the DNA separated from the particle, entered the cell nucleus, and produced enough adiponectin to significantly reduce the proliferation of new cells.

In a practical application, such nanoparticles could be magnetically directed into stents, the tiny, metal scaffolded tubes inserted into a patient's partially blocked vessels to improve blood flow. Many stents eventually fail as cells grow on their surfaces and create new obstructions, so delivering anti-growth genes to stents could help keep blood flowing freely.

"Many of our particles can be used for pharmaceutical agents and gene vectors," said Levy.

Nanotechnology has been a hot topic of discussion as of late. Randall Lutter, PhD, FDA deputy commissioner for policy urged the FDA to embrace the technology and to realize that there is an increased interest in nanotech (MDD, July 26, 2007).

During a July conference call Lutter said that the nanotechnology field "may provide new roots to deliver drug treatments to areas of the body that were inaccessible." Lutter also admits that the FDA is behind the nanotech curve and needs to play catch-up.

But while everyone seems to be repeating the nanotech mantra, high costs and one-sided representations of the new technologies could cause potential road blocks. During the National Academy of Sciences two-day conference Vikki Colvin PhD, professor of chemistry and chemical engineering at Rice University said it doesn't take much for the popular opinion of nanotech to change from "wow to yuck" (MDD April 12, 2007).

Levy, who has studied nanotechnology and nanoparticles since the early '90s, says he plans on riding out the technology's "wow factor." He said his team would look into further studies into the feasibility of using the nanoparticles for gene therapy in blood vessels damaged by vascular disease.

He suggested that the nanoparticles might find broader application, such as delivering gene therapy to tumors, or carrying drugs instead of or in addition to genes. Another possibility is that after preloading genetically engineered cells with nanoparticles, researchers could use magnetic forces to direct the cells to a target organ.

Additionally, researchers might deliver nanoparticles to magnetically responsive, removable stents in sites other than blood vessels, such as airways or parts of the gastrointestinal tract.

"We could remove the stent after the nanoparticles have delivered a sufficient number of genes, cells or other agents to have a long-lasting benefit," Levy said.

The nanoparticle study was funded by the National Institutes of Health, the Nanotechnology Institute (Philadelphia) and the William J. Rashkind Endowment of The Children's Hospital of Philadelphia.