Targeted delivery of doxorubicin to human breast cancers by folate-decorated star-shaped PEG–PCL micelle

Abstract

Conventional nanocarriers are associated with systemic toxicity and poor bioavailability of the anti-tumor drugs due to undesired specificity. The objective of this study is to introduce a folic targeting ligand on the surface of a polymeric nanocarrier to enhance the delivery of the doxorubicin (DOX) via ligand-mediated endocytosis. Hence, the folate decorated-micelle based on the star-shape FOL–PEG–PCL copolymer was synthesized. The chemical structure of the copolymer was characterized by proton nuclear magnetic resonance spectroscopy, gel permeation chromatography and differential scanning calorimetry, respectively. A generalized biocompatibility test of the micelle was evaluated using MTT assay, in vitro hemolytic test, nitric oxide production and reactive oxygen species generation, respectively. When DOX was encapsulated in the micelle, the drug loading efficiency and drug loading content were found to be 90% and 13%, respectively. The average particle size of the DOX-loaded micelle, determined by dynamic light scattering was 148.2 nm. The intracellular uptake experiments showed that human breast cancer cells (MCF-7) could uptake a similar amount of DOX from two dosage forms: free DOX and DOX-loaded FOL–PEG–PCL micelle. The uptake of DOX-loaded FOL–PEG–PCL micelle was higher than that of free DOX in MCF-7/adr cells, adriamycin-resistant cell line. The uptake of the micelle in MCF-7 was found to be time-dependent; e.g.caveolae/lipid-raft mediated endocytosis and then folate receptor-mediated endocytosis was observed. This study demonstrates that the FOL–PEG–PCL micelle was non-toxic and the DOX-loaded FOL–PEG–PCL micelle could be a potential carrier for cancer treatments.