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: Mingrong Cheng, Hongzhi Xu, Yong Wang, Houxiang Chen, Bing He, Xiaoyan Gao, Yingchun Li, Jiang Han, Zhiping Zhang
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 7 Pg. 1287-99 ( 2013) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 24187487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Antimetabolites, Antineoplastic
• Delayed-Action Preparations
• Drug Carriers
• Interleukin-2
• Interferon-gamma
• Chitosan
• Glycyrrhetinic Acid
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, pharmacology)
• Cell Proliferation (drug effects)
• Chitosan (chemistry)
• Delayed-Action Preparations
• Dose-Response Relationship, Drug
• Drug Carriers (chemistry)
• Female
• Fluorouracil (administration & dosage, pharmacology)
• Glycyrrhetinic Acid (chemistry)
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Killer Cells, Natural (metabolism)
• Liver Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Nanoparticles
• Particle Size
• Survival Rate
• T-Lymphocytes, Cytotoxic (metabolism)
• T-Lymphocytes, Regulatory (metabolism)
• Time Factors