Chitosan coated biocompatible zeolitic imidazolate framework ZIF-90 for targeted delivery of anticancer drug methotrexate

Abstract

In this work, using zeolitic imidazolate framework (ZIF) as carrier, a new biocompatible anti-cancer drug delivery system CS@MTX@ZIF-90 (CMZ) was efficiently synthesized by one-pot method. Methotrexate (MTX), an anticancer drug as folic acid analogue was loaded into ZIF-90 through Schiff base reaction between amino group in MTX and aldehyde group of imidazole-2-carboxaldehyde ligand with drug loading amount about 250 ​mg/g. As a pH-sensitive biomaterial, chitosan (CS) was modificated by the outer layer of the particles to improve the pH responsiveness of the composite CMZ during the drug release process. By releasing a large amount of MTX under acidic conditions (the pH environment around tumor cells), and releasing a substantially lower amount of MTX at a normal environment, CMZ exhibited a pH-responsive and target-selective behavior. In addition, in vitro cytotoxicity and anticancer activity results showed that CMZ can inhibit the growth of liver cancer HepG2 cells, prostate cancer DU145 ​cells and gastric cancer SGC7901 ​cells, with only negligible toxicity to normal EC304 ​cells. Based upon the results of corresponding experiments, CMZ exhibited high MTX drug loading, cancer-targeted release and good biocompatibility, which can be used as a good candidate for anticancer drug delivery system.