Development of Monocarboxylate Transporter 4 Inhibitor/Docetaxel-Loaded Multilayer Nanoparticles for Prostate Cancer Combination Therapy.

The proposed work seeks to develop and characterize a smart, multilayer MCT4i/DXT-loaded polylactide-glycolic acid nanoparticle for combination therapy in prostate cancer. The core of the smart LBL NPs is prepared by nanoprecipitation, and the sodium acetate "freeze-coating" technique is used to construct the multilayer nanoparticle. The size, zeta potential, entrapment efficiency, and nanoparticle surface chemistry are characterized by Malvern Panalytical Advanced Zeta Sizer. UV/VIS Spectrophotometer, transmission electron microscopy (TEM), and Fourier Transform Infrared spectrometer (FT-IR). The cytotoxicity of the different nanoformulations is assessed in the C4-2 cell line by MTS assay, and the mechanism of cell death is assessed by flow cytometry using an apoptosis assay. The TEM shows a multi-layer spherical nanoparticle. The multilayer nanoparticle is 255.539 nm in size, with an entrapment efficiency of 89.56 ± 1. 70% and 91.55 ± 7.82% for compound AZD0095 and docetaxel, respectively. The FTIR confirms that sodium acetate coats all the nanoformulation. Low-dose combination therapy effectively inhibits C4-2 cell growth. Smart nanoparticles exhibit dose-dependent cytotoxicity in C4-2 cells. Cell death occurs via apoptosis with docetaxel alone and via secondary necrosis with the combination therapy. The multilayer nanoparticle is a promising nanomedicine for combination therapy in prostate cancer.