Anticancer activity of released doxorubicin from a folate-mediated polyelectrolyte complex.
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.
Chiu
Chien Chih
CC
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Lin
Yin Tzu
YT
Sun
Shuo Li
SL
Sung
Kuo Hsun
KH
Wang
Li Fang
LF
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*
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