Targeted nanoparticle delivery of tumor suppressing UDP‐glucuronosyltransferase (UGT) genes into cancer cells

• Published in: The FASEB journal Vol. 24; no. S1; p. 520.5
• Main Authors: Radominska‐Pandya, Anna, Karmakar, Alokita, Bratton, Stacie M., Yang, Xu, Mahmood, Mena W., Gallus‐Zawada, Anna E., Biris, Alexandru S.
• Format: Journal Article
• Language: English
• Published: Federation of American Societies for Experimental Biology 01-04-2010
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.24.1_supplement.520.5

We propose the use of nanostructural materials as carriers for the delivery of proteins, genes, growth factors, or other biological systems into cancer cells. Normal cells express a set of UGTs that control the steady state concentration of ligands for nuclear receptors. However, UGT mRNA and protein levels are downregulated or completely absent in several cancer tissues such as those in the breast, ovary and pancreas. We hypothesize that specific UGTs, which catalyze the detoxification and deactivation of biologically active compounds, can be specifically targeted to cancer cells using nanoparticles both in vitro and in vivo and can become an effective tool in cancer treatment. For these studies, we have used single wall carbon nanotubes (20 μg/ml) attached to a UGT expression plasmid to form the CNT/UGT active bio‐nano systems. Specific in‐vitro delivery of these nanosystems by using growth factors and monoclonal antibodies to various cancer cell lines (pancreatic Panc1) was also proved. The incubation of CNT/UGT particles with Panc1 cells for 24 hours resulted in phenotype changes in the cells and eventually death as measured by Caspase 3 activity. It can be concluded that the CNT/UGT system was extremely bio‐active and induced all the cancer cells to die. Experiments with ovarian and breast cancer cell lines are underway. (NIH‐GM075893 to AR‐P; ASTA 08‐CAT‐03 to ASB).