After binding DNA segments to tiny iron-containing spheres called nanoparticles, researchers have used magnetic fields to direct the nanoparticles into arterial muscle cells, where the DNA could have a therapeutic effect.
Although the research, done in cell cultures, is in early stages, it may represent a new method for delivering gene therapy to benefit blood vessels damaged by arterial disease.
The nanoparticles are extremely small, ranging from 185 to 375 nanometers (a nanometer is one billionth of a meter, or a millionth of a millimeter). For comparison, red blood cells are ten to 100 times larger. The researchers were able to control the nanoparticle size by varying the amount or composition of solvents they used to form the nanoparticles.
The magnetically driven delivery system also may find broader use as a vehicle for delivering drugs, genes or cells to a target organ. "This is a novel delivery system, the first to use a biodegradable, magnetically driven polymer to achieve clinically relevant effects," said study leader Robert J. Levy, M.D., the William J. Rashkind Chair of Pediatric Cardiology at The Children's Hospital of Philadelphia. "This system has the potential to be a powerful tool."
The proof-of-principle study, performed on vascular cells in culture, appears in the August issue of the FASEB Journal, published by the Federation of American Societies for Experimental Biology.
Impregnated with iron oxide, the nanoparticles carry 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 here 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, expandable metal scaffolds 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.
The materials composing the nanoparticles are biodegradable, so they break down into simpler, nontoxic chemicals that can be carried away in the blood. "Previous researchers had shown that magnetically driven nanoparticles could deliver DNA in cell cultures, but ours is the first delivery system that is biodegradable, and therefore, safer to use in people," said Levy.