December 18, 2006
Inorganic Nanoparticles Improve Gene Transfer into Cells
Though gene therapies hold great promise for treating cancer, it has proven difficult to deliver therapeutic genes efficiently into cancer cells. Animal studies have shown that polymeric and lipid-based nanoparticles have the potential to overcome this delivery obstacle, and at least one nanoparticle-based gene therapy is in human clinical trials. Now, thanks to research conducted at Carnegie-Mellon University and the University of Pittsburgh, gene therapy researchers have yet another nanoscale tool at their disposal, this one made of biocompatible inorganic materials.
Charles Sfeir, D.D.D, Ph.D., at the University of Pittsburgh, and Prashant Kumta, Ph.D., of Carnegie Mellon University, led the team of investigators that developed calcium phosphate nanoparticles to function as stable gene carriers. The investigators published their work in the journal Biomaterials.
While other research teams have explored the use of calcium phosphate-based materials for gene delivery – calcium phosphate is the major mineral component and is biocompatible – these efforts have largely failed because the physical characteristics of these materials did not protect DNA from degradation and did not promote efficient uptake by cells. This group of investigators appears to have overcome these limitations by developing a new chemical method that allows them to carefully adjust the relative amounts of calcium and phosphorous in the nanoparticles.
This synthetic approach enabled the investigators to discern the optimal nanoparticle characteristics needed for maximum stability, gene loading into the nanoparticle, and delivery into cells. Based on these experiments, the investigators determined that calcium phosphate nanoparticles with a calcium-to-phosphorous ratio ranging from 100 to 300, i.e., between 100 and 300 calcium atoms for each atom of phosphorous in the nanoparticle, were the most efficient at delivering DNA into cells and having the delivered genes function within the cell. These nanoparticles, which ranged in size from 25 to 50 nanometers in diameter, were capable of binding large amounts of DNA and protecting the bound DNA from degradation.
This work is detailed in a paper titled, “Nanostructured calcium phosphates (NanoCaPs) for non-viral gene delivery: Influence of the synthesis parameters on transfection efficiency.” An investigator at the University of North Carolina also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.