title: Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells.
abstract: Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma.
authors.affiliation: Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China ; Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Cheng
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Houxiang
authors.initials: H
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Han
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010316:Particle Size; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007376:Interleukin-2; D007371:Interferon-gamma; D048271:Chitosan; D006034:Glycyrrhetinic Acid; D005472:Fluorouracil
keywords: 5-fluorouracil; glycyrrhetinic acid; hepatic carcinoma; regulatory T cells; targeted therapy