title: Anticancer activity of released doxorubicin from a folate-mediated polyelectrolyte complex.
abstract: Folic acid (FA) was selected to link with macromolecules for the selective and specific delivery of doxorubicin (DOX) to folate receptor (FR)-positive tumor cells, because of the high binding affinity of FA to the tumor-associated FR. We synthesized folate-mediated chondroitin sulfate (FA-PEG-ChS) for tumor cell targeting and non-folate-mediated naproxen-linked chondroitin sulfate (Nap-PEG-ChS) for comparison. Both the aforementioned polymers contain a PEG1000 spacer. We encapsulated an anticancer agent, DOX, during the formation of complexes with chitosan. Polyelectrolyte complexes (PEC) grafted with a fluorescent dye (FITC) served as a platform for online imaging cellular internalization. FR-positive KB and FR-deficient A549 cancer cells were tested. The concentration to kill 50% of the cells (IC(50)) of DOX-loaded FA-complex was 1.53 μg/ml, in comparison to 0.91 μg/ml of free DOX. The overlaid fluorescent images of DOX and FITC on confocal laser scanning microscopy demonstrated the co-internalization of DOX and the complex nanoparticles into the cytoplasm of KB cells followed by a gradual release of DOX.
authors.affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chien Chih
authors.initials: CC
authors.lastname: Chiu
authors.forename: Yin Tzu
authors.initials: YT
authors.lastname: Lin
authors.forename: Shuo Li
authors.initials: SL
authors.lastname: Sun
authors.forename: Kuo Hsun
authors.initials: KH
authors.lastname: Sung
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002234:Carbodiimides / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D005492:Folic Acid / Q000737:chemistry*; D058972:Folic Acid Transporters / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002234:Carbodiimides; D004337:Drug Carriers; D058972:Folic Acid Transporters; C074139:1-ethyl-3-(3-dimethylaminoethyl)carbodiimide; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002809:Chondroitin Sulfates; D005492:Folic Acid