29 Feb Experimental 3DNA Nanocarrier Used to Target and Treat Ovarian Tumor Cells
MedicalResearch.com Interview with:
Janet A. Sawicki, Ph.D.
Deputy Director and Professor
Lankenau Institute for Medical Research
100 Lancaster Ave.
Wynnewood, PA 19096
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Sawicki: This study is the first to demonstrate the versatility of the 3DNA nanocarrier for in vivo targeted delivery of a cancer therapeutic. It supports the notion that HuR is a promising therapeutic target, and supports the potential use of FA-derivatized 3DNA dendrimer for siHuR targeted delivery to ovarian tumor cells for treatment of advanced ovarian cancer patients.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Sawicki: 3DNA is a highly versatile nanocarrier that can be easily conjugated to a variety of therapeutic molecules (DNA, siRNA, mRNA, miRNA, small molecule drugs) as well as to targeting moieties (peptides, antibodies) allowing for targeted delivery of therapeutics to target organs and/or tumors following systemic administration. Opportunities abound for preclinical development of this novel nanocarrier platform for the delivery of single agents or combinations of therapeutics for the treatment of many diseases.
Cancer Res. 2016 Feb 26. pii: canres.2073.2015.
Delivery of therapeutics targeting the mRNA-binding protein HuR using 3DNA nanocarriers suppresses ovarian tumor growth.
Huang YH1, Peng W2, Furuuchi N2, Gerhart JV3, Rhodes K3, Mukherjee N4, Jimbo M5, Gonye GE6, Brody JR7, Getts RC3, Sawicki JA8.
Dr. Janet Sawicki (2016). Experimental 3DNA Nanocarrier Used to Target and Treat Ovarian Tumor Cells