Magnetic and temperature-sensitive solid
lipid particles (mag. SLPs) were prepared in the presence of
oleic acid-coated
iron oxide (IO-OA) nanoparticles with
1-tetradecanol and poly(
ethylene oxide)-block-poly(ε-
caprolactone) as
lipid and stabilizing
surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian
cancer cell lines and their drug-resistant counterparts using
trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human
leukemia cell lines growing in
suspension (Jurkat and HL-60/wt), as well as the
doxorubicin (Dox)- and
vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human
glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the
fluorescent dyes Hoechst 33342 and
propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed
chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the
Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related
proteins, study of DNA fragmentation (
DNA laddering due to the inter-nucleosomal cleavage and
DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and
Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or
necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the
reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly,
hydrogen peroxide and
superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20-40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat
iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human
tumor cells, including drug-resistant ones.