The potential role of hot flashes treatment strategies and regorafenib combinations in breast cancer therapy via co-drug loaded polymeric nanoparticles

Abstract

This research investigates the possible combinations of anticancer drug regorafenib (Rego) and hot flashes syndrome treatment drugs medroxyprogesterone acetate (Mdp), fluoxetine (Flu) or venlafaxine (Ven) for treating breast cancer. According to the calculated dose reduction index (DRI), it requires 5.34–12.83-fold less Rego plus 6.78–35.01-fold less Flu to achieve the same inhibition at 1 μM Rego: 5 μM Flu (1:5) ratio, this indicates that the combination therapy enhances the cytotoxic property. Hence, Rego-Flu (1:5) was selected for optimum combination therapy; the delivery of exact synergic drug combinations of both drugs in targeted tissue has to be ensured. Therefore, we used nanoparticles made of mPEG-b-PLGA. Prepared nanoparticles presented high uniformity (PDI is 0.023 for Rego loaded nanoparticles (Rego@mPEG-b-PLGA) and 0.038 for Rego + Flu loaded nanoparticles (Rego + Flu_ mPEG-b-PLGA)) with a diameter of 213.8 ± 16.5 nm for Rego _ mPEG-b-PLGA and 225.5 ± 7.3 nm for Rego + Flu@mPEG-b-PLGA. Rego + Flu@mPEG-b-PLGA increased the late apoptotic cell ratio (6.38 % for MCF-7 and 10.98 % for MDA-MB-231 cells). The changes at the molecular level were investigated with metabolomics studies, and our findings indicate that when breast cancer cells were treated with Rego@mPEG-b-PLGA and Rego + Flu@mPEG-b-PLGA, particular changes were observed in glycolysis and the tricarboxylic acid cycle (TCA) mechanisms. The combination of these drugs influenced critical metabolic pathways, suggesting its potential as an effective treatment strategy for breast cancer.