Magnetic Temperature-Sensitive Solid-Lipid Particles for Targeting and Killing Tumor Cells

Abstract

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 Ś więtek et al.Magnetic Solid-Lipid Particles 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.

Ferrite Nanoparticles-Based Reactive Oxygen Species-Mediated Cancer Therapy

“…Horak et al prepared magnetic and temperature-sensitive solid lipid particles (mag. SLPs) using oleic acid-coated iron oxide, 1-tetradecanol, and poly(ethylene oxide)-block-poly(E-caprolactone), which could melt down in the tumorous tissue to produce more ROS than the non-magnetic SLPs and neat iron oxides, inducing apoptosis of Jurkat leukemic cells (Swietek et al, 2020 ). Sawant et al developed novel pH responsive and mitochondria targeted poly-l-lysine-coated Fe 3 O 4 @FePt core shell nanoparticles (Mito-PANPs) (Pandey et al, 2020 ).…”

Hybrid Magnetic Lipid-Based Nanoparticles for Cancer Therapy

“…Magnetic SLN were studied for colon adenocarcinoma [ 100 ], cancer in general [ 101 , 102 , 103 ], and in inflammatory process [ 104 ]. The SLN are also used as a contrast agent for magnetic resonance imaging application.…”

Magnetic Solid Nanoparticles and Their Counterparts: Recent Advances towards Cancer Theranostics

“…Different metals and metal derivatives such as iron oxide, gold, and gadolinium [ 74 , 83 , 95 , 96 , 97 , 98 , 99 ] have been incorporated in the nanoformulations producing novel platforms with great potential in cancer therapy and tissue imaging. In particular, encapsulated iron oxide and gadolinium have been studied abundantly as magnetic delivery systems that can be guided to tumor regions and/or activated for controlled drug release and cell ablation (magnetic hyperthermia) via an external magnetic field or by endogenous stimuli such as pH changes [ 168 , 169 , 170 , 171 ]. In particular, iron oxide nanoparticles are considered biocompatible and safe materials and are the gold standard magnetic nanoparticles in medical research, despite the fact that they are able to cause cytotoxicity from the generation of ROS species via the Fenton reaction, which can lead to the damage of DNA, lipids, proteins, and carbohydrates [ 171 , 172 ].…”

“…Altogether, the mSLNs have been demonstrated to be promising tools because of their good biocompatibility [ 171 , 172 , 179 ], improvement of thermo-responsiveness compared to SLNs [ 168 ], efficiency in targeting tumors [ 174 , 181 ], and their high drug encapsulation efficiency. Furthermore, these nanosystems allow the application of magnetic hyperthermia as a means to provide thermal therapy and control drug release [ 164 , 172 , 181 ], in addition to being used as MRI contrast agents [ 174 , 181 ].…”