Combination of anti-miR19a-3p polyplex plus doxorubicin for breast cancer in 2D culture and apoptosis assay in 3D spheroids in a microwell device

Abstract

One of the most common cancers and a main cause of death worldwide among women is breast cancer (BC). Combination therapy is being widely investigated to reduce the dose of chemotherapy drugs, prevent the development of drug resistance, and improve treatment outcomes. Here we tested PEI-PBA-SAP-F15 (PPSF) polymeric nanoparticles to efficiently deliver a microRNA antagonist (anti-miR19a-3p) to BC cell lines. We evaluated the combination of anti-miR19a-3p plus doxorubicin (DOX) in both 2D and 3D cell cultures. We cultured 3D tumor spheroids in an innovative microfluidic device that was fabricated using a 3D printing system. The PPSF polyplexes had the correct size and zeta potential to efficiently transfer anti-miR19a-3p into MCF7 cells. The expression level of phosphatase and tensin homolog (PTEN), the attainment gene of microRNA-19a-3p was increased. PTEN up-regulation inhibited cell migration and caused cell cycle arrest. Apoptosis was also significantly induced with the combination treatment. Confocal microscopy studies revealed that the population of dead cells was in an important degree higher in MCF7 spheroids transfected with anti-miR19a-3p-PPSF plus DOX.