Synthesis, characterization, cellular uptake and cytotoxicity of a multifunctional magnetic nanocomposite for the targeted delivery and controlled release of doxorubicin to cancer cells

The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects towards healthy tissue. To overcome this, in this study a novel drug delivery system, namely, carboxymethyl chitosan capped magnetic nanoparticle intercalated montmorillonite nanocomposites (CMCS-capped-MNP/MMT) was developed and characterized by transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, small-angle X-ray scattering, zeta potential analysis and a superconducting quantum interference device. The optimum pH value for the encapsulation of doxorubicin (DOX) into CMCS-capped-MNP/MMT was examined. The controlled release behavior of DOX was examined at 5.0 and 7.4 pH. The release rate of the loaded drug molecules was slow at pH 7.4 but increased significantly at acidic pH 5.0. The cytotoxicity of DOX-loaded-CMCS-capped-MNP/MMT towards MCF-7 cancer cells was investigated. The results showed that DOX-loaded-CMCS-capped-MNP/MMT retained significant antitumor activities. The cellular uptake of the fluorescent coumarin 6-loaded CMCS-capped-MNP/MMT on HeLa cells was analyzed with confocal laser scanning microscopy (CLSM) and flow cytometry and the results showed that MMT enhanced the cellular uptake efficiency. The effects of DOX and DOX-loaded-CMCS-capped-MNP/MMT on H9c2 cell death were investigated by using a microplate reader. The heating characteristics of the magnetic nanocomposites were investigated in a high frequency alternating magnetic gradient; a stable maximum temperature of 45 degrees C was successfully achieved within 40 min. The study demonstrated that CMCS-capped-MNP/ MMT is not only a good delivery system for DOX but also appears to be a promising strategy for protecting against oxidative injury observed in DOX induced cardiotoxicity.