Doxorubicin and BikDD delivery to AU565 breast cancer cell line by targeted polymeric nanocarriers

Joint Event on 28^th International Conference on Cancer Research and Anticancer Therapies & International Conference on Oncogenesis & Oncologic Emergency Medicine & 3^rd International Conference on Tumor & Cancer Immunology and I

September 17-18, 2018 | San Diego, USA

Zeynep Busra Bolat, Umut Can Oz, Ayca Ece Nezir, Umut Ugur Ozkose, Ozgur Yilmaz, Asuman Bozkir, Dilek Telci and Fikrettin Sahin

Yeditepe University, Turkey
Ankara University, Turkey
Marmara Research Center, Turkey
Piri Reis University, Turkey
Istanbul Technical University, Turkey

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Breast cancer is the most common cancer type among women with a 25.1 percent incidence worldwide. It is a major public health problem with no current effective treatment thus more target-specific therapeutic methods are needed. Peptide 18, a tumor homing peptide, shown to have high potential in targeting breast cancer cells was used in labeling the polymeric nanocarrier constructs formulated poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) (PEtOx-b-PLA) based polymers. These polymers have high biocompatibility and biodegradable characteristics. Toxicology studies showed that these polymeric nanocarriers did not affect the cell survival of human endothelial cells (HUVEC), hepatocytes (HEPG2), mesenchymal stem cell, human osteoblasts (hFOB1.19), kidney (HEK293) and fibroblasts cell lines, characterizing these constructs with minimal toxicity. Target specificity and cellular uptake of peptide 18 labeled polymeric nanocarriers were determined via flow cytometry and confocal microscopy. Our results showed that these targeted polymeric nanocarriers possessed higher binding affinity to AU565 breast cancer cell line compared to healthy epithelial MCF10A breast cell line. Pro-apoptotic BikDD gene and doxorubicin drug were loaded to these targeted polymeric nanocarriers. In order to examine BikDD gene delivery by targeted polymeric nanocarriers in AU565 cells, qPCR and western blotting was conducted. The increased Bik mRNA and protein expression levels in these AU565 cells suggest the high effectiveness of the targeting polymeric nanocarriers. The apoptotic activity of pro-apoptotic BikDD gene and doxorubicin delivery by peptide 18 labeled polymeric nanocarriers to AU565 cells was detected using Annexin V/PI staining and Caspase 3 colorimetric assay. Our results showed an enhanced apoptotic rate in AU565 cells. Following in vitro studies, the delivery of doxorubicin using polymeric nanocarriers were analyzed in CD-1 nude mice animal model. The animal study suggested that doxorubicin delivery by peptide 18 labeled polymeric nanocarriers significantly decreased tumor volume by 3 fold when compared to the 2 fold decrease recorded for doxorubicin alone. However, there was no significant difference in tumor volume of CD-1 nude mice treated with BikDD gene loaded into peptide 18 labeled polymeric nanocarriers. Our results suggest that this targeted therapy may potentially become a substitute for the conventional approaches. This project is funded by TUBITAK (213M726-231M760).

Biography :

E-mail: zeynep@gmail.com