03 June 2013

A new means of gene delivery: magnetic nanoparticles

NanoNewsNet based on EurekAlert! – New gene delivery method: magnetic nanoparticlesVascular stenting saves the lives of many thousands of patients, but this method is not without side effects and complications, such as arterial restenosis and thrombosis.

The June issue of The FASEB Journal reports on the development of a new method of gene delivery via nanoparticles, which allows solving many problems associated with the use of gene therapy vectors and preventing complications accompanying stenting (Chorny et al., Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors). The new strategy uses stents as a platform for targeted gene delivery. Genes are delivered to cells at the sites of arterial injuries without causing undesirable side effects, including systemic ones.

Gene therapy is a promising strategy for the treatment of vascular diseases. Nevertheless, its translation into clinical practice requires pharmaceutical carriers capable of providing effective site-specific delivery, as well as long-term expression of transgenes in blood vessels. Although the adenovirus, deprived of the ability to replicate, has several important advantages as a vector for vascular gene therapy, its clinical use is limited by rapid inactivation – one of the key problems of any gene therapy method, insufficiently effective delivery to vascular cells and serious side effects. The researchers suggested that magnetic nanoparticles (MNPs) loaded with adenovirus, based on zinc oleate, will increase the efficiency of transferring genetic material into artery cells and protect adenoviruses from inactivation by neutralizing factors.

"This study can help overcome a number of barriers to the translation of experimental gene therapy approaches into clinical practice," says Michael Chorny, PhD, a participant in the study, from the Department of Cardiology of the Abramson Pediatric Research Center at the Children's Hospital of Philadelphia in Pennsylvania. "Bringing gene therapy closer to clinical use is a step towards developing safer and more effective treatments for cardiovascular diseases."

To demonstrate the possibility of effective gene delivery without causing side effects by means of biocompatible magnetic nanoparticles, Dr. Cherny and his colleagues first conducted a series of experiments with vascular (endothelial and smooth muscle) cells in vitro. Despite the difficulties that have always accompanied the delivery of genes to these cells, their studies have shown that under magnetic conditions, the nanoparticles loaded with genes effectively delivered their cargo, especially compared to conventional gene therapy vectors.

The researchers then switched to targeted gene delivery using their nanoparticles to the stented arteries of rats. The expression of targeted genes delivered to the stent in such animals was significantly higher than in control group rats, which were injected with either an equivalent dose of adenoviruses or non-magnetic nanoparticles. In addition, magnetic nanoparticles made it possible to achieve significantly more active gene expression in stented arteries compared to other organs and tissues.

"This is a new and very interesting approach, showing that investments in various fields of fundamental science pay off over time," Gerald Weissmann, MD, editor–in-chief of The FASEB Journal, commented on the success of the group. "When the first nanoparticles were developed and when the first gene of a human disease that can be corrected was identified, no one could have imagined that these two achievements would one day unite to save lives."

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