Cytotoxic effect of thermosensitive magnetoliposomes loaded with gemcitabine and paclitaxel on human primary breast cancer cells (MGSO-3 line)

Abstract

Magnetic hyperthermia therapy may be combined with controlled release of multiple chemotherapeutic agents to effectively treat cancerous tumors. This study describes the preparation and characteristics of gemcitabine- and paclitaxel-loaded magnetoliposomes to investigate the in vitro potential of this formulation in association with magnetic hyperthermia therapy to control drug delivery. Magnetic nanoparticles, gemcitabine, and paclitaxel were encapsulated into thermosensitive liposomes with efficiency of 84%, 57%, and 68%, respectively. The hydrodynamics and distribution of the magnetoliposome formulations were determined, showing ideal characteristics for accumulation in the tumor tissue: mean size less than 100 nm, polydispersity index < 0.2, and stability in aqueous suspension for at least 15 days. At physiological temperature, only 9% of the gemcitabine and 1% of the paclitaxel were released after 72 h, but the formulations exposed to an alternating magnetic field (AMF) dissipated energy sufficient to increase mean temperature to 43 °C in just 5 min and delivered 94% of the gemcitabine and 43% of the paclitaxel after 30 min. In vitro cytotoxicity and magnetic hyperthermia studies were then carried out using human primary breast cancer cells (MGSO-3) and MTT assay. The viability of cells exposed to the loaded magnetoliposomes and AMF for 30 min fell to 27%; the cells treated with the loaded magnetoliposomes but not exposed to AMF exhibited viability over 60%, while hyperthermia alone (with unloaded magnetoliposomes) reduced cell viability to 50%. This study consequently suggests that gemcitabine- and paclitaxel-loaded magnetoliposomes may present potential for combined treatments involving hyperthermia and controlled release of chemotherapeutic drugs.