Fe3O4/chitosan nanocomposite for magnetic drug targeting to cancer

Abstract

Magnetic nanoparticles have been introduced in the cancer arena to optimize the accumulation of the drug dose into the tumor interstitium by means of a magnetic gradient. As a result, the chemotherapeutic agent may exhibit an enhanced anticancer efficacy and a negligible systemic toxicity. In these contexts, we have used the coacervation methodology for the design of magnetite/chitosan (core/shell) nanocomposites. The heterogeneous structure of these multifunctional nanoparticles allows the possibility of their use in drug delivery thanks to their excellent responsiveness to magnetic gradients. A detailed characterization of these nanocomposites (including electron microscopy observations, infrared spectrometry, electrophoresis, and thermodynamic analysis) suggested a complete polymeric coverage of the magnetite nuclei. The magnetic responsiveness of the magnetite/chitosan nanoparticles was quantitatively investigated by the hysteresis cycle and qualitatively confirmed by microscopic visualization of the performance of the nanocomposite suspensions under exposure to a 1.1 T permanent magnet. This nanodevice has been used to enhance the intravenous delivery of the anticancer agent gemcitabine to the cancer tissue. Compared to the surface adsorption technique, gemcitabine entrapment into the polymeric shell yielded higher drug loading values, and a slower drug release profile. Heating characteristics of the nanocomposites have been investigated in a high frequency alternating magnetic gradient: a stable maximum temperature of 45 °C was successfully achieved within 30 min. Finally, an in vivo proof of concept using Prussian blue staining has further confirmed the magnetic targeting capabilities of this magnetite/chitosan core/shell nanodevice. Thus, the here described stimuli-sensitive nanomedicine possesses important characteristics, such as magnetically targeted drug delivery, high drug loading and low burst release, as well as hyperthermia inducing capability, indicating its potential for effective therapy of cancer.