title: Molecularly targeted co-delivery of a histone deacetylase inhibitor and paclitaxel by lipid-protein hybrid nanoparticles for synergistic combinational chemotherapy.
abstract: In this study, a transferrin-anchored albumin nanoplatform with PEGylated lipid bilayers (Tf-L-APVN) was developed for the targeted co-delivery of paclitaxel and vorinostat in solid tumors. Tf-L-APVN exhibited a sequential and controlled release profile of paclitaxel and vorinostat, with an accelerated release pattern at acidic pH. At cellular levels, Tf-L-APVN significantly enhanced the synergistic effects of paclitaxel and vorinostat on the proliferation of MCF-7, MDA-MB-231, and HepG2 cancer cells. Vorinostat could significantly enhance the cytotoxic potential of paclitaxel, induce marked cell apoptosis, alter cell cycle patterns, and inhibit the migratory capacity of cancer cells. In addition, Tf-L-APVN showed prolonged circulation in the blood and maintained an effective ratio of 1:1 (for paclitaxel and vorinostat) throughout the study period. In HepG2 tumor-bearing mice, Tf-L-APVN displayed excellent antitumor efficacy and the combination of paclitaxel and vorinostat significantly inhibited the tumor growth. Taken together, dual drug-loaded Tf receptor-targeted nanomedicine holds great potential in chemotherapy of solid tumors.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Hima Bindu
authors.initials: HB
authors.lastname: Ruttala
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Poudal
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Yongjoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Jeonghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, South Korea.
authors.forename: Sae
authors.initials: S
authors.lastname: Kwang Ku
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Chul
authors.initials: C
authors.lastname: Soon Yong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Oh Kim
mesh_terms: D018248:Adenoma, Liver Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008055:Lipids; D000077337:Vorinostat; D017239:Paclitaxel
keywords: albumin; histone deacetylase inhibitor; lipid bilayer; paclitaxel; transferrin