Magnetic nanoparticles double wrapped into cross-linked salep/PEGylated carboxymethyl cellulose; a biocompatible nanocarrier for pH-triggered release of doxorubicin

Int J Biol Macromol. 2020 May 8:158:994-1006. doi: 10.1016/j.ijbiomac.2020.05.040. Online ahead of print.

Abstract

A magnetic nanocarrier was synthesized in which Fe3O4 nanoparticles were encapsulated into double layers of polysaccharide shells. The first shell, which was composed of cross-linked salep polysaccharide, contained multiple nitrogen atoms in its structure and provided numerous sites for multiple functionalization. A fluorescence dye and doxorubicin, as widely used chemotherapy agent, were easily attached to the first shell and then a second shell of PEGylated carboxymethyl cellulose enveloped the drug loaded carrier to enhance its biocompatibility and regulates the drug release behavior. The results of drug loading and release behavior showed that the resulting nanocarrier can carry large amounts of drug molecules and a remarkable pH-sensitive release was observed in vitro. The hemolysis and coagulation assays proved the biocompatibility of nanocarrier toward red blood cells and the MTT experiments confirmed that the drug loaded nanocarrier is highly toxic for MCF-7 cancer cells while the unloaded nanocarrier was almost nontoxic. Further flow cytometry experiments and confocal microscopy demonstrated that the double layered magnetic nanocarrier can penetrate into the cells and efficiently release the drug molecules into the cell nucleus. Moreover, the results of MRI experiments performed on the nanocarrier showed that it can be serve as a negative MRI contrast agent.

Keywords: Doxorubicin; Drug delivery system; Magnetic nanocarrier.