title: Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells.
abstract: The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(DL-lactide-co-glycolide)/poly(ethylene glycol) copolymer.
  
  
  
  Vorinostat-NPs exhibited spherical shapes with sizes <100 nm. Vorinostat-NPs have anticancer activity similar to that of vorinostat in vitro. Vorinostat-NPs as well as vorinostat itself increased acetylation of histone-H3. Furthermore, vorinostat-NPs have similar effectiveness in the suppression or expression of histone deacetylase, mutant type p53, p21, and PARP/cleaved caspase-3. However, vorinostat-NPs showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat, whereas empty nanoparticles had no effect on tumor growth. Furthermore, vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed histone deacetylase (HDAC) expression in vivo. The improved antitumor activity of vorinostat-NPs can be explained by molecular imaging studies using near-infrared (NIR) dye-incorporated nanoparticles, i.e. NIR-dye-incorporated nanoparticles were intensively accumulated in the tumor region rather than normal one.
  
  
  
  Our results demonstrate that vorinostat and vorinostat-NPs exert anticancer activity against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Thus, we suggest that vorinostat-NPs are a promising candidate for anticancer chemotherapy in cholangiocarcinoma. Graphical abstract Local delivery strategy of vorinostat-NPs against cholangiocarcinomas.
authors.affiliation: Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 602-739, Republic of Korea. teichi80@gmail.com.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kwak
authors.affiliation: School of Medicine, Pusan National University, Yangsan, Gyeongnam, 626-770, Republic of Korea. biokimdh@gmail.com.
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 602-739, Republic of Korea. nanomed@naver.com.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.affiliation: Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 602-739, Republic of Korea. sulsulpul@naver.com.|Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam, 626-770, Republic of Korea. sulsulpul@naver.com.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D005453:Fluorescence; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D000077337:Vorinostat; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat