4.2 Article

Iron Speciation in Animal Tissues Using AC Magnetic Susceptibility Measurements: Quantification of Magnetic Nanoparticles, Ferritin, and Other Iron-Containing Species

Journal

ACS APPLIED BIO MATERIALS
Volume 5, Issue 5, Pages 1879-1889

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsabm.1c01200

Keywords

magnetic nanoparticles; quantification; iron; ferritin; animal models; magnetic measurements

Funding

  1. Ministerio de Ciencia, Innovacion y Universidades (MCIU)
  2. Agencia Estatal de Investigacion (AEI)
  3. Fondo Europeo de Desarrollo Regional (FEDER) [PGC2018-096016-B-I00]
  4. European Commission [814439, DT-NMBP-02-2018]
  5. MagicCellGene Project (M-ERA.NET call 2016 - Ministerio de Economia y Competitividad, MINECO, Spain) [PCIN-2017-060]
  6. Fondos FEDER [E15_17R]
  7. MINECO [RYC-2015-17640, RYC-2014-15512, RYC2019-026860-I]
  8. Gobierno de Aragon [E15_17R]
  9. FSE/Agencia Estatal de Investigacion [RYC-2015-17640, RYC-2014-15512, RYC2019-026860-I]
  10. H2020 Societal Challenges Programme [814439] Funding Source: H2020 Societal Challenges Programme

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This study utilized AC magnetic susceptibility measurements to analyze the impact of single intratumor administration of magnetic nanoparticles on different organs in an animal model, detailing the quantification of iron associated with the nanoparticles and the analysis of other endogenous iron-containing species. The technique allows for minimal tissue sample preparation, characterization of large amounts of tissue, tracking of nanoparticle transformations with high specificity, and achieving low limits of detection for certain iron-containing species.
The simultaneous detection and quantification of several iron-containing species in biological matrices is a challenging issue. Especially in the frame of studies using magnetic nanoparticles for biomedical applications, no gold-standard technique has been described yet and combinations of different techniques are generally used. In this work, AC magnetic susceptibility measurements are used to analyze different organs from an animal model that received a single intratumor administration of magnetic nanoparticles. The protocol used for the quantification of iron associated with the magnetic nanoparticles is carefully described, including the description of the preparation of several calibration standard samples of nanoparticle suspensions with different degrees of dipolar interactions. The details for the quantitative analysis of other endogenous iron-containing species such as ferritin or hemoglobin are also described. Among the advantages of this technique are that tissue sample preparation is minimal and that large amounts of tissue can be characterized each time (up to hundreds of milligrams). In addition, the very high specificity of the magnetic measurements allows for tracking of the nanoparticle transformations. Furthermore, the high sensitivity of the instrumentation results in very low limits of detection for some of the iron-containing species. Therefore, the presented technique is an extremely valuable tool to track iron oxide magnetic nanoparticles in samples of biological origin.

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