title: Treatment by serum up-conversion nanoparticles in the fluoride matrix changes the mechanism of cell death and the elasticity of the membrane.
abstract: Nanoparticles are increasingly being used for treatment and diagnostic purposes, but their effects on cells is not fully understood. Here, the interaction of fluorescent up-conversion nanoparticles (UpC-NPs) with neutrophils was investigated by imaging and measurement of membrane-cytosceletal elasticity by atomic force microscopy. It was found that UpC-NPs induce the death of neutrophils mainly by necrosis, and to a smaller extent by a novel process called 'mummification'. Necrosis occurs by gradual loss of intracellular contents and nuclei, 45-110min after exposure to UpC-NPs. Mummification is apparent as an increase in the rigidity of the neutrophils' membrane and acquisition of a characteristic bumpy shape with numerous protrusions; this structure does not change during atomic force microscopy scanning. Coating UpC-NPs with protein by incubation with serum leads to (1) formation of nanoparticle aggregates in the nm and μm size range, (2) a reduction in toxicity, (3) reduced mummification of neutrophils, and (4) no significant reduction of the elasticity of the membrane-cytoskeletal complex of neutrophils 30min after exposure to coated UpC-NPs. The study shows that serum proteins greatly curb the toxicity of nanoparticles and reveals mummification as a novel mechanism of UpC-NP-induced cell death.
authors: Research and Education Center "Physics of Solid State Nanostructures", Lobachevski Nizhny Novgorod State University, Avenue Gagarina 23, 603950 Nizhny Novgorod, Russian Federation. Electronic address: pleskova@mail.ru.
authors: Svetlana N
authors: SN
authors: Pleskova
authors: Research and Education Center "Physics of Solid State Nanostructures", Lobachevski Nizhny Novgorod State University, Avenue Gagarina 23, 603950 Nizhny Novgorod, Russian Federation.
authors: Ekaterina N
authors: EN
authors: Gorshkova
authors: Department of Molecular Biology and Biomedicine, Lobachevski Nizhny Novgorod State University, Avenue Gagarina 23, 603950 Nizhny Novgorod, Russian Federation.
authors: Viktor V
authors: VV
authors: Novikov
authors: Department of Clinical Research, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
authors: Marc
authors: M
authors: Solioz
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects; D004548:Elasticity / Q000187:drug effects; D005453:Fluorescence; D005459:Fluorides / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D044967:Serum
chemical_list: D005459:Fluorides
keywords: Atomic force microscopy; Membrane elasticity; Neutrophil granulocytes; Up-conversion nanoparticles; Young’s modulus