Nanotech News

December 12, 2005

Lipid Nanoparticles Rerouted to Deliver Drugs to Tumor Cells

Low-density lipoproteins (LDL), commonly known as the carriers of “bad cholesterol,” are notorious for the role they play in the development of heart disease. Investigators at the University of Pennsylvania School of Medicine hope to turn bad into good by using these naturally occurring nanoparticles to develop a targeted nanoparticle capable of delivering drugs to tumors. The promising results of this research team’s initial work appear in the Proceedings of the National Academy.

Gang Zheng, Ph.D., and his colleagues have taken a strategy that causes LDL nanoparticles to be rerouted away from their usual cellular receptors to those found on the surface of tumor cells. To accomplish this rerouting, the investigators determined what it was about LDL particles that enabled them to bind to their normal receptors so that they could alter that property. The investigators found that certain amino acids on the surface of the LDL particles were key to binding the LDL receptor, and that they could chemically treat just those amino acids and eliminate that binding characteristic without altering the natural cargo-carrying capacity of the LDL nanoparticle. The investigators also developed a method of linking the cancer-cell targeting folic acid to the modified nanoparticles.

In vitro tests with several types of cancer cells growing in culture showed that these modified particles did indeed bind to folic acid receptors on cancer cells rather than their normal receptors. The particles were also capable of carrying agents used in photodynamic therapy into the tumor cells. The one potential limitation of this work that the researchers noted is that the method they use to reroute the LDL particles could make them visible to the immune system, which native LDL particles are not. The investigators plan further studies to characterize the behavior of the modified particles in an intact animal.

This work, funded by National Cancer Institute, is detailed in a paper titled, “Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents.” This work was published online in advance of print publication. An abstract is available through PubMed.
View abstract.