Novel Role of Bone-Targeted Cabazitaxel Nanoparticles: Beyond the Classical Taxane Function in Metastatic Prostate Cancer Cells




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Bone-metastatic prostate cancer symbolizes the beginning of the end-stage disease. Bone is the primary metastatic site for prostate cancer, a condition correlated to low five-year overall survival rates, extreme pain, and poor quality of life. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. I hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuate the EMT marker, Vimentin, and lead to an increase in E-cadherin expression, which imparts epithelial characteristics to cells and inhibits cancer progression of advanced prostate cancer to distant sites. I observed the reduction of phosphorylated Src at tyrosine 416 along with increased expression of phosphorylated cofilin, cofilin at serine 3, which could affect migration and invasion pathways in cancer cells. Both increased expression of p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for prostate cancer by inhibiting invasion, migration, and EMT in prostate cancer cells. Finally, I discuss an ongoing project that also targets bone metastatic PCa with a different strategy, a liposomal drug delivery system.