Liposome-Fe3O4-Doxorubicin Mediated Treatment of Melanoma Tumors

Abstract

Purpose: Magnetic hyperthermia is a treatment method based on eddy currents, hysteresis, and relaxation mechanisms of magnetic nanoparticles (MNPs). MNPs such as Fe3O4 have the ability to generate heat under an alternating magnetic field. Heat sensitive liposomes (Lip) convert from lipid layer to liquid layer through heat generated by MNPs and can release drugs. In this research we explore whether combining liposomes, Doxorubicin (DOX) and Magnetic Nanoparticles could help magnetic hypothermia treatment be even more effective in treating cancerous tumors. Methods: In this study, different groups of DOX, MNPs and liposomes were evaluated. The superparamagnetic nano materials were synthesized by co-precipitation method. The MNPs, DOX and a combination of MNPs and DOX were efficiently loaded into the liposomes using the evaporator rotary technique. Magnetic properties, microstructure, specific absorption rate in MNPs, zeta potential, loading percentage of the MNPs and DOX concentration in liposomes, in vitro drug release of liposomes were studied. Finally, the necrosis percentage of cancer cells in C57BL/6J mice bearing melanoma tumors was assessed for all groups. Results: The loading percentages of MNPs and concentration of DOX in the liposomes were 18.52 and 65% respectively. The average size of Lip-DOX-MNPs obtained was 460 nm. The Lip-DOX-MNPs at the buffer citrate solution, showed highly specific absorption rate as the solution temperature reached 42°C in 5 min after exposure to alternative magnetic field. The release of DOX occurred in a pH-dependent manner. The volume of tumor in the therapeutic groups containing the MNPs significantly decreased compared to the others. Numerical analysis showed that the tumor volume in mice receiving Lip-MNPs-DOX was 9.29% that of the control and a histological examination of the tumor section showed 70% necrosis. Conclusion: The Lip-DOX-MNPs could be effective agents which reduce malignant skin tumors growth and increase cancer cell necrosis.