The synthesis of LA-Fe3O4@PDA-PEG-DOX for photothermal therapy–chemotherapy

Abstract

A facile methodology is presented to construct a multifunctional nanocomposite that integrates photothermal therapy and specific drug release into a single nanostructure. Firstly, magnetic Fe₃O₄@polydopamine core–shell nanoparticles (Fe₃O₄@PDA) were synthesized via a reversed-phase microemulsion approach. By varying the amount of DA, Fe₃O₄@PDA with a particle size of 28–38 nm can be obtained. To further ensure the monodispersity, biocompatibility and specific uptake, PEG and lactobionic acid (LA) were grafted onto Fe₃O₄@PDA (LA-Fe₃O₄@PDA-PEG), whose fast photothermal conversion is derived by the combination of Fe₃O₄ and PDA with high near infrared (NIR) absorption. Then, doxorubicin hydrochloride (DOX) was adopted as the typical anticancer drug, which was loaded onto LA-Fe₃O₄@PDA-PEG via electrostatic and π–π stacking interaction. The release kinetics investigation further demonstrated the acid/heat-triggered DOX release. HepG2 cells (hepatocellular cell line) were used as the target cancer cells, and the fast uptake was due to the nanoparticle size and abundant asialoglycoprotein receptors on HepG2 cells. Besides, an external magnetic field also can improve the uptake, especially when the magnet is placed at the bottom of the cell disk. The enhanced specific cytotoxicity toward HepG2 cells was also ascribed to the synergistic effect of chemo- and photothermal therapy. Based on the novel properties, the LA-Fe₃O₄@PDA-PEG-DOX nanocomposite showed its potential application in hepatocyte therapy.