Alginate based tamoxifen/metal dual core-folate decorated shell: Nanocomposite targeted therapy for breast cancer via ROS-driven NF-κB pathway modulation

Breast cancer endocrine resistance prevents unleashing full capabilities of Tamoxifen (TMX), besides TMX off-target side effects on healthy tissue. In this study, we engineered TMX nanocomposite via co-loading it on alginate-based silver nanoparticles and embedding within folic acid-polyethylene glycol surface conjugate. The coating process was done by w/o/w double emulsion method. To confirm the silver nanoparticles formation, UV spectroscopy, XRD and TEM analysis were carried out. TEM results confirmed the core-shell structure of folate targeted nanocomposite with approximate average diameter of 66 nm, the nanocomposite structures were characterized by FTIR, TGA and SEM. By comparing with the non-targeted formula, folate decorated formula had 12-folds lowered IC50 value and 12.5–14-fold higher cancer cells toxic selectivity index. Also, after 4 h treatment, both fluorescence microscopic and flow cytometric analysis indicated higher intracellular accumulation of folic acid conjugated formula on MCF-7 cancer cells than the non-targeted one with 3.44-folds. The breast cancer cytotoxic effects of this metal-endocrine nanocomposite formula could be explained by the induction of reactive oxygen species (ROS), down regulation of survival oncogenic genes (BCL-2 and Survivin) and the accumulation of MCF-7 cells in G2/M phase. All these data confirm the efficiency and efficacy of the formulated nanocomposite as future treatment for breast cancer.