Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

Autor: Marcelo de las Heras, Marta Pérez-Hernández, Sebastián Menao, María Moros, Grazyna Stepien, Beatriz Pelaz, Eva M. Galvez, Pablo del Pino, Jesús M. de la Fuente, Scott G. Mitchell, Julián Pardo, Maykel Arias
Přispěvatelé: Universidad de Zaragoza, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), European Research Council, European Commission, Gobierno de Aragón, Alexander von Humboldt Foundation, Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Física de Partículas
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
Health
Toxicology and Mutagenesis
Cell
Metal Nanoparticles
Apoptosis
02 engineering and technology
Toxicology
Cell morphology
01 natural sciences
Biodistribution
Tissue Distribution
Nanotoxicology
Cell Line
Transformed
Membrane Potential
Mitochondrial
Gold nanoprisms
Chemistry
General Medicine
021001 nanoscience & nanotechnology
3. Good health
Cell biology
Mitochondria
medicine.anatomical_structure
Toxicity
Injections
Intravenous
ROS generation
Female
Inflammation Mediators
0210 nano-technology
Cell physiology
Primary Cell Culture
lcsh:Industrial hygiene. Industrial welfare
010402 general chemistry
Mitochondrial membrane-potential
Risk Assessment
Interferon-gamma
In vivo
lcsh:RA1190-1270
medicine
Animals
Humans
Cell Shape
lcsh:Toxicology. Poisons
Cell Proliferation
A549 cell
Cell growth
Tumor Necrosis Factor-alpha
Research
0104 chemical sciences
Mice
Inbred C57BL
Cell culture
A549 Cells
Gold
Reactive Oxygen Species
lcsh:HD7260-7780.8
HeLa Cells
Zdroj: Particle and Fibre Toxicology
Particle and fibre toxicology 14 (2017). doi:10.1186/s12989-017-0222-4
info:cnr-pdr/source/autori:Perez-Hernandez M.; Moros M.; Stepien G.; del Pino P.; Menao S.; de las Heras M.; Arias M.; Mitchell S.G.; Pelaz B.; Galvez E.M.; de la Fuente J.M.; Pardo J./titolo:Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo/doi:10.1186%2Fs12989-017-0222-4/rivista:Particle and fibre toxicology/anno:2017/pagina_da:/pagina_a:/intervallo_pagine:/volume:14
Particle and Fibre Toxicology, Vol 14, Iss 1, Pp 1-20 (2017)
Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Digital.CSIC. Repositorio Institucional del CSIC
ISSN: 1743-8977
Popis: [Background]: The special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection.
[Methods]: Cellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration.
[Results]: Internalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period.
[Conclusion]: Our data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health.
This work was supported by the MAT2011–26851-CO2–01, MAT2011–26851-CO2–02, SAF2011–25390, SAF2014–54763-C2–1-R and SAF2014–54763-C2–2-R - projects of the Spanish Ministry of Science and Innovation, PIE201460I019 (CSIC), the grant ERC-Starting Grant 239931-NANOPUZZLE project, ERC-PoC 754609 HOTFLOW project, Fondo Social Europeo (FSE; Gobierno de Aragón) and the Consellería de Cultura, Educación e Ordenación Universitaria (Centro singular de investigación de Galicia accreditation 2016–2019, ED431G/09) and the European Regional Development Fund (ERDF). P.d.P., J.M.F., J.P. thank ARAID for financial support, B.P. thanks the Alexander von Humboldt Foundation for a fellowship and M.M. acknowledges financial support from European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 660228.
Databáze: OpenAIRE
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