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.