Overcoming Multidrug Resistance in Prostate Cancer Cells Using Nanoparticle Delivery of a Two-Drug Combination

Prostate cancer (PCa) is the second most diagnosed cancer in men. The resistance of prostate cancer to chemotherapy has been linked to the ATP Binding Cassette (ABC)-Mediated Multidrug Resistance (MDR). This study investigated the combination of 3-Bromopyruvate (3-BPA) and the anti-inflammatory molecule SC-514 in reducing MDR in prostate cancer. The compounds were incorporated into a PLGA nanoparticles to increase delivery to target cells.
To investigate the effectiveness of SC-514 and/3-BPA, cytoxicity assays including trypan blue dye exclusion, MTT tetrazolium reduction, NBT, LDH release poly caspase detection, cell titer glow assay, and ELISA were utilized. Both immunofluorescence and multidrug resistance efflux assays were utilized to estimate the number of drug resistant cells. SC-514 was encapsulated in PLGA nanoparticles via single-emulsion method. SC-514 nanoparticles were analyzed utilizing Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Liquid chromatography–mass spectrometry (LC–MS) was used to measure the amount of SC- 514 released from the nanoparticle. Alternative SC-514 drug release quantification methods such as colony forming assay, wound healing assay, and transwell and migration assay were explored.