Suppressing Cancer Cell Signaling Through Nanoparticle Delivery of
Antagonistic Antibodies or Nucleic Acids
In the past few decades, cancer researchers have identified several critical signaling pathways that are overactive in cancer cells relative to normal cells and that are responsible for driving tumor growth, resistance to conventional therapies, and recurrence. For example, many cancer cells have commandeered the developmental Wnt and Hedgehog signaling pathways to support their survival and self-renewal capacity. Suppressing these signaling pathways is a promising strategy to improve patient outcomes, but the key mediators of these pathways are challenging to target with small molecule therapeutics due to lack of an effective binding site. My research group is developing nanoparticles that can suppress these “undruggable” signaling pathways through the selective delivery of antagonistic antibodies or small interfering ribonucleic acid (siRNA) molecules. Our antibody-coated nanoparticles halt signal transduction by binding specific receptors to lock them in a ligand-unresponsive state, and our siRNA-coated nanoparticles regulate gene expression by delivering siRNA into the cell cytoplasm where it initiates degradation of specific messenger RNA molecules. Each of these nanoparticle platforms exploits the unique multivalent properties that arise when biomolecules are arranged in a three-dimensional manner on a nanoparticle carrier. In this presentation, I will describe the results of our in vitro studies with these antibody and siRNA nanocarriers, using aggressive breast and brain cancers as example disease models.