title: Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy.
abstract: A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (-5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Qu
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Liu
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Congyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Research Center for Multicomponent Traditional Medicine and Microecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Research Center for Multicomponent Traditional Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D031742:Coix / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D005690:Galactose / Q000138:chemical synthesis* / Q000737:chemistry; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D012639:Seeds; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D004952:Esters; D005690:Galactose
keywords: antihepatoma; coix seed oil; coixan; hepatic targeting; multicomponent-based microemulsion; oral drug delivery system