Combination eEF2K gene and drug delivery for treatment of breast cancer

Abstract

Eukaryotic elongation factor 2 kinase (eEF2K) is overexpressed in a wide variety of cancer types, including hormone receptor positive breast cancer. Targeting of eEF2K has demonstrated anti-tumor activity with the potential of enhanced treatment efficacy in combination with chemotherapy. Here, we describe gold nanoparticle (AuNPs) based delivery of siRNAs enabling eEF2K knockdown in combination with doxorubicin (DOX) to estrogen receptor (ER) positive breast cancer (MCF7) cells. The siRNAs and DOX were co-delivered on the same NP or delivered on separate NPs in a mixture at various siRNA:drug ratios. Effective inhibition of eEF2K expression was provided together with delivery of DOX leading to the enhanced inhibition of cancer cell proliferation compared to DOX delivery alone. siRNA:DOX ratio of 1:2.25 demonstrated synergistic inhibition of cancer cell proliferation. Delivery of eEF2K siRNAs and DOX on separate NPs showed anti-proliferative activity superior to co-delivery on the same NP. These results suggest that eEF2K inhibition enhanced the anticancer activity of chemotherapy on MCF7 breast cancer cells and that the delivery method of the therapeutics had an influence on cytotoxicity.