Synergistic anticancer activity of combined histone deacetylase and proteasomal inhibitor-loaded zein nanoparticles in metastatic prostate cancers

Abstract

The development of resistance and subsequent metastasis makes prostate cancer a leading cause of cancer-related death among men. Hence, nanoparticle-based combination chemotherapeutics could be a viable treatment strategy. Weaimed to prepare vorinostat (Vor) and bortezomib (Bor) combination-loaded zein nanoparticles (ZNP, ZNP/VB) for treating metastatic prostate cancers. Our results revealed the successful preparation of ZNP/VB with a small particle size (similar to 160 nm) and polydispersity index (similar to 0.20). Importantly, controlled and pH-dependent drug release profiles were observed. ZNP/VB exhibited high uptake in different prostate cancer cells and, thereby, exhibited higher cytotoxicity and apoptosis. Additionally, the enhanced anti-migration effect of and induction of pro-apoptotic proteins by ZNP/VB suggest its potential effectiveness in cancer treatment. ZNP/VB showed enhanced in vivo antitumor effects compared to that observed for each free drug and their combination, with minimal toxicity. Taken together, ZNP/VB could be a potential formulation for the effective treatment of metastatic prostate cancers. (C) 2016 Elsevier Inc. All rights reserved.