Evaluation of poly (2-ethyl-2-oxazoline) (petox)-based multifunctional carrier systems for breast cancer targeted therapy

Breast cancer is the major cause of death in females with the highest incidence rate worldwide. It is categorized as a public health problem with no current effective treatment, thus more target specific therapeutic methods are required. Tumor homing peptides show a high potential in targeting cancer, and Peptide 18 shows a high targeting specificity toward breast cancer. Thus, it was used in labeling three different nanocarrier constructs: PEtOx-DOPE liposome, PEtOx-b-PLA polymersome, and PEtOxPEIPCL micelles. These polymers have high biocompatibility, biodegradability and low toxicity characteristics. Toxicology studies showed that these nanocarrier formulations did not affect the cell survival of HUVEC, kidney HEK293, mesenchymal stem cell, and normal epithelial breast cells, characterizing these constructs with minimal toxicity. Target specificity and cellular uptake studies indicate that the Peptide 18-targeted nanocarriers possessed higher binding affinity to breast cancer AU565 line compared to the normal epithelial breast MCF10A cell line. These targeted nanocarriers were then used as carriers for the pro-apoptotic BikDD gene and doxorubicin. High effectiveness of the targeting nanocarriers in AU565 cells was determined with increase of mRNA expression levels of Bik leading to apoptosis. Furthermore, treatment of doxorubicin loaded peptide 18 labeled nanocarriers showed enhanced apoptotic activity in AU565 cells. Following in vitro studies, the delivery of pro-apoptotic BikDD gene and doxorubicin using nanocarriers were analyzed in CD-1 nude mice animal model. The animal study suggested that doxorubicin delivery by peptide 18 labeled nanocarriers significantly decreased tumor volume when compared to doxorubicin treatment alone. Although, there was a decrease in tumor volume of CD-1 female nude mice treated with BikDD gene loaded into peptide 18 labeled nanocarriers, it was not significant. Our results suggest that this breast cancer targeted therapy has the potential to become a substitute for current conventional approaches. This project is funded by TUBITAK (213M726).