Introduction: The development of theranostic systems could improve the quality of cancer treatment. Biocompatible Fe3O4 nanoparticles can be used in contrast agents and hyperthermia preparations. Doxorubicin (DOX) is the antitumor agent in the system. However, the surface modification of the developed systems is necessary for safe and prolonged circulation in the bloodstream. This study compared the influence of polymer shell composition on DOX release and particle stability in a saline solution. We analyzed polymers such as chitosan, polyethylene glycol (steric hindrance), and lysozyme.
Methods: We prepared Fe3O4 nanoparticles using the hydrothermal method. The synthesized particles were examined using SEM, EDX, FTIR, and BET analysis systems. The magnetic characteristics and surface charge of the nanoparticles were also studied. DOX loading and release were investigated using spectrophotometric methods at different pH values (5.5, 7.4, and 8.5). The coating techniques of the developed systems with polymer shells were optimized. The DOX release kinetics of coated particles at different pHs were investigated. Polymer-coated particles provide pH-dependent drug release due to the swelling–shrinking behavior of polymers. The cytotoxicity of the obtained systems was evaluated through in vitro tests using the cancer Emt6 cell line and the NIH 3T3 healthy cell line.
Results: The obtained nanoparticles (20 nm) were superparamagnetic. We determined the DOX loading capacity of the particles to be 15%. The particles demonstrated a high percentage of drug release (80%) at pH=5.5, whereas drug release was nearly absent in neutral and alkaline solutions. All types of polymer coatings provided particle stability and prolonged drug release. The chitosan shell demonstrated the highest colloidal stability, while the largest release rate (40%) was shown by lysozyme. Fe3O4 particles loaded with doxorubicin exhibited cytotoxicity to both cell lines, but the coating application reduced the cytotoxic effect on healthy cells.
This research was funded by the Russian Science Foundation (№20-19-00120_P).
