Dendrimers are chemically synthesized nanoparticles in which a branching monomer is polymerized to give tree-like structures organized around a central molecule, resulting in an atomically defined, more or less spherical nanostructure. The presence of many functional chemical groups on the dendrimer surface means these particles can easily be modified with molecules that provide added functionality to the dendrimer, such as molecules that target particular cells, and chemotherapy drugs as cargoes. Researchers at the University of Michigan have demonstrated in a model using immunocompromised mice (so that they do not reject human tumors) that dendrimers targeted to tumors and carrying anti-cancer drugs show great promise as potential therapy for head and neck cancer. From the National Cancer Institute Alliance for Nanotechnology in Cancer “Polymeric Nanoparticles Attack Head and Neck Cancer“:
Head and neck cancer, the sixth most common cancer in the world, has remained one of the more difficult malignancies to treat, and even when treatment is successful, patients suffer severely from the available therapies. Now, researchers at the University of Michigan have developed a tumor-targeted nanoparticle that delivers high doses of anticancer agents directly to head and neck tumors. Tests in animals have shown that this novel formulation increases survival while triggering fewer side effects.
Reporting its work in the Journal of Oral and Maxillofacial Surgery [abstract], a team led by James R. Baker, Jr., created a spherical polymeric nanoparticle known as a dendrimer to deliver the drug methotrexate to head and neck tumors. To target the nanoparticle to those tumors, the investigators decorated the nanoparticle’s surface with folic acid. Many tumors, but few healthy cells, produce excessive amounts of a folic acid receptor on their surfaces. …
The researchers tested their dendrimer-based formulation in three different groups of mice. The control group had tumors grown from human head and neck tumors that did not produce the folic acid receptor. The two experimental groups had tumors grown from human head and neck tumors that expressed moderate and high levels of the folic acid receptor. Mice receiving the equivalent of three times the normally lethal dose of methotrexate, delivered on the dendrimer nanoparticle experienced none of the weight loss normally associated with methotrexate therapy. More importantly, dendrimer-delivered therapy produced marked gains in therapeutic response even in the mice whose tumors produced only moderate levels of folic acid receptor.
Some additional information on targeted dendrimer cancer therapeutics is available from the Michigan Nanotechnology Institute for Medicine and Biological Sciences, including a free review article “Dendrimer-based nanoparticles for cancer therapy“.
