title: Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.
abstract: There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction.
authors.affiliation: Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
authors.forename: Nipaporn
authors.initials: N
authors.lastname: Ngernyuang
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kean 40002, Thailand; Comprehensive Cancer Research Group, Faculty of Medicine, Khon Kaen University, Khon Kean 40002, Thailand.
authors.forename: Wunchana
authors.initials: W
authors.lastname: Seubwai
authors.affiliation: Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Sakda
authors.initials: S
authors.lastname: Daduang
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Patcharee
authors.initials: P
authors.lastname: Boonsiri
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Temduang
authors.initials: T
authors.lastname: Limpaiboon
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: jurpoo@kku.ac.th.
authors.forename: Jureerut
authors.initials: J
authors.lastname: Daduang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D005492:Folic Acid; D005472:Fluorouracil
keywords: Cancer; Cholangiocarcinoma; Folate receptor; Nanomedicine; Targeted therapy