Background:
Nanotechnology is emerging as a promising tool to target cancer cells. Gold nanoparticles (GNPs) are preferentially taken up by cancer cells when injected into the blood stream and their safety has been demonstrated in human clinical trials. WSU researchers have designed a unique nanoparticle conjugate that combines a GNP with a small molecule inhibitor (SMI#9) to treat triple negative breast cancer and melanoma by targeting RAD6, an important protein involved in DNA damage tolerance and canonical Wnt signaling. RAD6 is an ubiquitin-conjugating enzyme that is overexpressed in aggressive and chemoresistant cancer cells. The SMI#9 inhibitor blocks ubiquitinating activity of RAD6 and enhances sensitivity of cancer cells to DNA damaging chemotherapeutics. As a GNP conjugate, SMI#9 inhibits tumor growth as a monotherapy and enhances platinum drug sensitivity in combination treatments. For aggressive or metastatic cancers such as triple negative breast cancers that do NOT express conventional markers for targeted drug delivery, targeting RAD6 provides a powerful new approach for cancer treatment. Using nano-conjugates to selectively deliver drugs to the tumor cells will greatly reduce the toxic side effects of chemotherapy and improve outcomes.
Highlights:
* Selectively targeting TNBC and melanoma through the DNA repair and canonical Wnt pathway
* Cancer Therapeutics/Avoids potential for drug resistance response
* Reduces undesired side effects/Drug Nanodelivery
Stage of Development:
Preclinical/Animal Data
Publications:
* Pharmacological targeting of Rad6 enzyme-mediated translasion synthesis overcomes resistance to platinum-based drugs. J Biol Chem. 2017 Jun 23;292(25):10347-10363
* Gold nanoparticle conjugated Rad6 inhibitor induces cell death in triple negative breast cancer cells by inducing mitochondrial dysfunction and PARP-1 hyperactivation: Synthesis and characterization. Nanomedicine. 2016 Apr 12(3):745-57
Patent Status: Patent Pending
Licensing Opportunity: This technology is available for License