title: 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. We aimed 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 (~160nm) and polydispersity index (~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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Thapa
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Hanh Thuy
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Korean Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Pharmacy, Hanyang University, Ansan, Republic of Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. Electronic address: csyong@yu.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000069286:Bortezomib / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D004357:Drug Synergism; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D061988:Proteasome Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000077337:Vorinostat; D015028:Zein / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D061988:Proteasome Inhibitors; D000077337:Vorinostat; D000069286:Bortezomib; D015028:Zein
keywords: Bortezomib; Prostate cancer; Vorinostat; Zein nanoparticles