title: Real-Time Analysis of Magnetic Hyperthermia Experiments on Living Cells under a Confocal Microscope.
abstract: Combining high-frequency alternating magnetic fields (AMF) and magnetic nanoparticles (MNPs) is an efficient way to induce biological responses through several approaches: magnetic hyperthermia, drug release, controls of gene expression and neurons, or activation of chemical reactions. So far, these experiments cannot be analyzed in real-time during the AMF application. A miniaturized electromagnet fitting under a confocal microscope is built, which produces an AMF of frequency and amplitude similar to the ones used in magnetic hyperthermia. AMF application induces massive damages to tumoral cells having incorporated nanoparticles into their lysosomes without affecting the others. Using this setup, real-time analyses of molecular events occurring during AMF application are performed. Lysosome membrane permeabilization and reactive oxygen species production are detected after only 30 min of AMF application, demonstrating they occur at an early stage in the cascade of events leading eventually to cell death. Additionally, lysosomes self-assembling into needle-shaped organization under the influence of AMF is observed in real-time. This experimental approach will permit to get a deeper insight into the physical, molecular, and biological process occurring in several innovative techniques used in nanomedecine based on the combined use of MNPs and high-frequency magnetic fields.
authors: Laboratoire de Physique et Chimie des Nano-Objets (LPCNO), Université de Toulouse, INSA, UPS, F-31077 Toulouse, France and CNRS, UMR 5215, F-31077, Toulouse, France.
authors: Vincent
authors: V
authors: Connord
authors: Université de Toulouse 3, EA, 4552, Toulouse, France.
authors: Pascal
authors: P
authors: Clerc
authors: Laboratoire de Physique et Chimie des Nano-Objets (LPCNO), Université de Toulouse, INSA, UPS, F-31077 Toulouse, France and CNRS, UMR 5215, F-31077, Toulouse, France.
authors: Nicolas
authors: N
authors: Hallali
authors: Université de Toulouse 3, EA, 4552, Toulouse, France.
authors: Darine
authors: D
authors: El Hajj Diab
authors: Université de Toulouse 3, EA, 4552, Toulouse, France.
authors: Daniel
authors: D
authors: Fourmy
authors: Université de Toulouse 3, EA, 4552, Toulouse, France.
authors: Véronique
authors: V
authors: Gigoux
authors: Laboratoire de Physique et Chimie des Nano-Objets (LPCNO), Université de Toulouse, INSA, UPS, F-31077 Toulouse, France and CNRS, UMR 5215, F-31077, Toulouse, France.
authors: Julian
authors: J
authors: Carrey
mesh_terms: D002470:Cell Survival; D003199:Computer Systems; D004705:Endocytosis; D006801:Humans; D006979:Hyperthermia, Induced; D042541:Intracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D060526:Magnetic Fields; D018613:Microscopy, Confocal / Q000379:methods*; D008904:Miniaturization; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: cell death; confocal microscopy; magnetic hyperthermia; magnetic nanoparticles; reactive oxygen species