High-content screening as a universal tool for fingerprinting of vytotoxicity of nanoparticles

As researchers develop an ever-expanding toolkit of nanoparticles for use as drug and imaging agent delivery vehicles, there is a growing need to understand how a given nanoparticle's physical and chemical properties affect biological activity and toxicity.

Now, two researchers working independently of one another have develop new methods for measuring the biological activity of nanomaterials in a highly systematic manner that enable them to draw important insights about nanomaterial biologic activity.

Reporting its work in the Proceedings of the National Academy of Sciences of the United States of America, a research group lead by Ralph Weissleder, M.D., Ph.D., co-principal investigator of the MIT-Harvard Center of Cancer Nanotechnology Excellence, and Stuart Schreiber, Ph.D., of the Broad Institute of Harvard and MIT, describes its development of a broad panel of in vitro assays that measure a variety of nanoparticle properties. They then use a technique known as hierarchical clustering that identifies nanomaterials that have similar biological effects across a wide range of assays. This approach enabled the investigators to create strong structure-activity relationships that correlate nanoparticle properties to biological activities.

In the experiments reported in this paper, the investigators tested some 50 different nanomaterials. They used four different cell lines for their assays and measured biological activity at four different nanoparticle doses. The large amount of data generated by this type of extensive analysis enabled the researchers to identify different relationships with a high degree of statistical significance. This analysis clearly showed that there were definite correlations between the physical and chemical properties of a nanoparticle and biological activity. More importantly, the investigators found that the relationships identified using in vitro assays correlated with activity observed when the nanoparticles were administered to test animals.

Taking a similar approach, Nicholas Kotov, Ph.D., of the University of Michigan and Yurii Gun'ko, Ph.D., of Trinity College Dublin, led a team of investigators that developed a series of high-content screening assays for use in testing the cytotoxicity of a large number of quantum dots and gold nanoparticles. These assays, the researchers note, enabled them to distinguish subtle differences in cytotoxicity among similar nanomaterials, which should set the stage for conducting multiparametric analyses on large numbers of particles in a rapid and quantitative manner. The investigators are now working to modify their assay protocols to include biological properties such as transport across the cell membrane.

The work from the team headed by Dr. Weissleder and Dr. Schreiber, which was supported by the NCI's Alliance for Nanotechnology in Cancer, is detailed in the paper "Perturbational Profiling of Nanomaterial Biologic Activity." An abstract of this paper is available at the journal's Web site. View abstract

The work from the team led by Dr. Kotov and Dr. Gun'ko is detailed in the paper "High-Content Screening as a Universal Tool for Fingerprinting of Cytotoxicity of Nanoparticles." An abstract of this paper is available at the journal's Web site. View abstract