Pluronic F127–chondroitin sulfate micelles prepared through a facile method for passive and active tumor targeting

Abstract

Tumor-specific drug delivery is still a challenge in cancer therapy. Passive tumor targeting strategies, such as the enhanced permeability and retention (EPR) effect, cause nanocarriers to accumulate in tumors. However, this strategy can not provide specific tumor targeting. In this study, Pluronic F127 (PF127), a block copolymer which can inhibit drug efflux transporters in cancer therapy, was modified to form tumor-specific micelles with a natural polysaccharide, chondroitin sulfate (ChS), which imparts the site-specific property. A facile and efficient method based on Schiff base reaction was developed to facilitate both basic and clinical research. A series of PF127–ChS micelles with different ratios of PF127 and ChS were fabricated and evaluated in terms of size, morphology, drug loading efficiency and drug release behavior. Spherical micelles with a mean diameter of 155–241 nm were obtained. Their critical micelle concentration (CMC) was significantly reduced in contrast to PF127 micelles and their stability was enhanced. Doxorubicin (DOX) was loaded into the hydrophobic core of PF127 or adsorbed by ChS through electrostatic interactions with the negative charges of chondroitin sulfate. In vitro DOX release studies showed that DOX release from the micelles was enhanced at acidic pH values compared to physiological pH. A cytotoxicity assay (MTT) determined that the micelles possess significantly lower toxicity. Confocal microscopy and flow cytometry analysis indicated that DOX loaded micelles could efficiently release DOX inside cells by specific cellular uptake. These outcomes revealed that PF127–ChS micelles could be exploited as carriers for anti-tumor drugs for site-specific therapy of solid tumors.