May 1, 2006
Polymeric Nanoparticles Entrap Diverse Biological and Cancer Targeting Agents
In a novel twist on nanoparticle formation, a research team at the Northwestern University Center of Cancer Nanotechnology Excellence (CCNE) has developed a polymer nanoparticle that contains bioactive small molecules as part of its chemical structure. This new nanoparticle also contains reactive groups that allow tumor-targeting agents to be incorporated easily onto its surface.
SonBinh Nguyen, Ph.D., and Chad Mirkin, Ph.D., led a team of investigators that are exploring new methods for creating multifunctional nanoparticles for treating both hematological cancers, such as leukemia and lymphoma, and solid tumors. In this project, the results of which appear in the Journal of the American Chemical Society, the investigators focused on using polymers that contain bioactive molecules within their chemical structure as the material for forming nanoparticles.
To accomplish this feat, the investigators used a novel chemical approach known as ring-opening metathesis polymerization, or ROMP, that creates polymer molecules that fold upon themselves to create a so-called core-shell nanostructure. In this case, the core contains the bioactive segments of the polymer molecule while the shell contains reactive chemical groups that can be used to attach targeting molecules. The investigators attached both tumor-targeting antibodies and short segments of single stranded DNA to the outer surface of the polymer nanoparticle.
Tests on human breast cancer cells that overexpress the HER-2/neu proteins showed that nanoparticles decorated with anti-HER-2 antibodies were readily taken up by the cultured cells. In contrast, tumor cells lacking the HER-2/neu receptor did not take up the nanoparticles. Future experiments will now explore if the bioactive component of the nanoparticle can exert therapeutic effects once the nanoparticle enters a cell and unravels in the intracellular environment.
This work, which was supported in part by the National Cancer Institute’s Alliance for Nanotechnology in Cancer, is detailed in a paper titled, “Multifunctional polymeric nanoparticles from diverse bioactive agents.” An abstract of this paper is available through PubMed.