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Cited by 1,181Characterization and Applications of Magnetic NanoparticlesNanoparticle-Based Drug DeliveryIron Metabolism and Disorders

Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications

Open access
Dadfar, Seyed Mohammadali, Roemhild, Karolin, Drude, Natascha I., von Stillfried, Saskia, Knüchel, Ruth, Kiessling, Fabian, Lammers, Twan·2019·Advanced Drug Delivery Reviews
DOI 10.1016/j.addr.2019.01.005PMC PMC7115878
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Abstract

Many different iron oxide nanoparticles have been evaluated over the years, for a wide variety of biomedical applications. We here summarize the synthesis, surface functionalization and characterization of iron oxide nanoparticles, as well as their (pre-) clinical use in diagnostic, therapeutic and theranostic settings. Diagnostic applications include liver, lymph node, inflammation and vascular imaging, employing mostly magnetic resonance imaging but recently also magnetic particle imaging. Therapeutic applications encompass iron supplementation in anemia and advanced cancer treatments, such as modulation of macrophage polarization, magnetic fluid hyperthermia and magnetic drug targeting. Because of their properties, iron oxide nanoparticles are particularly useful for theranostic purposes. Examples of such setups, in which diagnosis and therapy are intimately combined and in which iron oxide nanoparticles are used, are image-guided drug delivery, image-guided and microbubble-mediated opening of the blood-brain barrier, and theranostic tissue engineering. Together, these directions highlight the versatility and the broad applicability of iron oxide nanoparticles, and indicate the integration in future medical practice of multiple iron oxide nanoparticle-based materials.

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Written from the paper’s full text.

TL;DR

This review summarizes synthesis, surface functionalization, characterization, toxicity, and diagnostic, therapeutic, and theranostic applications of iron oxide nanoparticles. It highlights clinical uses such as ferumoxytol for anemia, ferumoxsil for gastrointestinal imaging, and NanoTherm for magnetic fluid hyperthermia, alongside emerging theranostic strategies including companion diagnostics, microbubble-mediated blood-brain barrier opening, and tissue engineering.

Key findings

  • Diagnostic applications rely mainly on MRI T2/T2*-weighted contrast, with liver imaging using SPION of 50–150 nm hydrodynamic diameter, lymph node and inflammation imaging using USPIO of 20–30 nm, vascular imaging using VSOP around 7 nm, and FDA-approved oral ferumoxsil around 300 nm for gastrointestinal imaging.
  • Therapeutic uses include ferumoxytol, FDA-approved in 2009 for iron deficiency anemia in chronic kidney disease, and magnetic fluid hyperthermia with Nanotherm (15 nm, amino-silane coating); in recurrent glioblastoma, MFH plus radiotherapy gave median survival of 13.4 months versus 6.2 months in historical controls.
  • Iron oxide nanoparticles can shift tumor-associated macrophages toward an M1-like phenotype and increase reactive oxygen species, and they are being tested as companion diagnostics: ferumoxytol uptake correlated with response to irinotecan-loaded liposomes (Onivyde).
  • Theranostic applications include USPIO-loaded microbubbles for image-guided BBB opening, MPI tracking of ferucarbotran-labeled neuronal progenitor cells for up to 87 days, and labeled collagen scaffolds or vascular grafts visualized by MRI for up to 19–22 days.

Methods

  • Narrative review covering chemical synthesis routes (co-precipitation, thermal decomposition, microemulsion, sol-gel, hydrothermal, sonochemical, electrochemical), surface modification, characterization, and biocompatibility assessment of iron oxide nanoparticles.
  • Summarizes selected preclinical and clinical studies across diagnostic, therapeutic, and theranostic applications, including MRI, MPI, magnetic fluid hyperthermia, magnetic drug targeting, cell tracking, and tissue engineering.
  • No systematic search strategy, inclusion criteria, risk-of-bias assessment, or meta-analysis is described.

Limitations

  • Stated in the paper: several approved SPION were withdrawn because of alternative diagnostic probes and protocols; MFH requires removing metals in the head area and causes MRI artifacts; magnetic drug targeting has produced mixed results, needs strong magnetic fields, and only one magnetically targeted nanocarrier reached patients but was terminated in phase II/III.
  • Stated in the paper: active and magnetic targeting strategies have not yet been translated to the clinic, and many theranostic regenerative medicine concepts are not in clinical practice.
  • Evident from the text: as a narrative review, it does not provide a systematic synthesis or quantitative pooling of evidence, and many cited applications remain preclinical or early clinical, leaving long-term safety and clinical implementation uncertain.

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Registry

Crossref · 10.1016/j.addr.2019.01.005

Cites

268 of 268 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 221 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Physical and biosynthetic synthesis protocols together make up less than 10% of all SPION synthesis methods.

    “Together, physical and biosynthetic synthesis protocols make up for less than 10% of all SPION synthesis methods [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Wu W Wu Z Yu T Jiang C Kim W-S Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications Sci Technol Adv Mater 2015 16 023501 PMC5036481 27877761 source

      Not checked in the free run.

  • Premisecitation

    SPION can be produced by chemical, physical and biosynthetic methodologies.

    “SPION can be produced in several different ways, encompassing chemical, physical and biosynthetic methodologies [3, 25, 28, 29].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [3] Wu W Wu Z Yu T Jiang C Kim W-S Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications Sci Technol Adv Mater 2015 16 023501 PMC5036481 27877761 source

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    • cites [25] Laurent S Forge D Port M Roch A Robic C Vander Elst L Muller RN Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications Chem Rev 2008 108 2064 2110 18543879 source

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    • cites [28] Hasany S Ahmed I Rajan J Rehman A Systematic review of the preparation techniques of iron oxide magnetic nanoparticles J Nanosci Nanotechnol 2012 2 148 158 source

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    • cites [29] Sodipo BK Aziz AA Recent advances in synthesis and surface modification of superparamagnetic iron oxide nanoparticles with silica J Magn Magn Mater 2016 416 275 291 source

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  • Premisecitation

    Physical methods for SPION synthesis suffer from a lack of ability to control particle size in the nanometer range.

    “Physical methods, which include powder ball milling, electron beam lithography, aerosol and gas phase deposition suffer from the lack of ability to control the size of particles in the nanometer size range [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Sodipo BK Aziz AA Recent advances in synthesis and surface modification of superparamagnetic iron oxide nanoparticles with silica J Magn Magn Mater 2016 416 275 291 source

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  • Premisecitation

    Iron oxide nanoparticles are used for a wide variety of biomedical and bioengineering applications.

    “Iron oxide nanoparticles, which belong to the ferrimagnetic class of magnetic materials, are used for a wide variety of biomedical and bioengineering applications [1, 2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • Premisereasoning

    Amorphous SPION obtained from sonochemical synthesis need further heat-treatment after synthesis.

    “Thus, the obtained amorphous SPION need to be further processed by heat-treatment after they have been synthesized [3, 28, 46–48].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [3] Wu W Wu Z Yu T Jiang C Kim W-S Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications Sci Technol Adv Mater 2015 16 023501 PMC5036481 27877761 source

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    • cites [28] Hasany S Ahmed I Rajan J Rehman A Systematic review of the preparation techniques of iron oxide magnetic nanoparticles J Nanosci Nanotechnol 2012 2 148 158 source

      Not checked in the free run.

    • cites [46] Wu W He Q Jiang C Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies Nanoscale Res Lett 2008 3 397 21749733 PMC3244954 source

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    • cites [47] Sodipo BK Aziz AA One minute synthesis of amino-silane functionalized superparamagnetic iron oxide nanoparticles by sonochemical method Ultrason Sonochem 2018 40 837 840 28946493 source

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    • cites [48] Kim EH Ahn Y Lee HS Biomedical applications of superparamagnetic iron oxide nanoparticles encapsulated within chitosan J Alloys Compd 2007 434 633 636 source

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  • May combine two claims. 49
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    Findingreasoning

    A good correlation between dextran accumulation in the brain and iron oxide nanoparticle-based MR imaging information was observed, exemplifying that such theranostic microbubbles hold potential for image-guided drug delivery to the brain.

    “A good correlation between dextran accumulation in the brain and iron oxide nanoparticle-based MR imaging information was observed, exemplifying that such theranostic MB hold potential for image-guided drug delivery to the brain.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The shell of microbubbles can be loaded with iron oxide nanoparticles for image-guided drug delivery purposes.

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    Premisecitation

    Upon surface modification, superparamagnetic iron oxide nanoparticles (SPION) can be employed for magnetic resonance imaging, magnetic particle imaging, targeted delivery of drugs, proteins, antibodies and nucleic acids, hyperthermia, biosensing, tissue repair, and separation of biomolecules.

    “Upon surface-modification, the resulting superparamagnetic iron oxide nanoparticles (SPION) can be employed for magnetic resonance imaging (MRI) [4–8], magnetic particle imaging (MPI) [9–12], targeted delivery of drugs, proteins, antibodies, and nucleic acids [6, 7, 13, 14], hyperthermia [15–17], biosensing [18], tissue repair [19], and separation of biomolecules [20].”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [4] Jin R Lin B Li D Ai H Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications Curr Opin Pharmacol 2014 18 18 27 25173782 source

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    • cites [9] Khandhar AP Ferguson RM Arami H Krishnan KML Monodisperse magnetite nanoparticle tracers for in vivo magnetic particle imaging Biomaterials 2013 34 3837 3845 23434348 PMC3602155 source

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    • cites [10] Du Y Lai PT Leung CH Pong PW Design of superparamagnetic nanoparticles for magnetic particle imaging (MPI) Int J Mol Sci 2013 14 18682 18710 24030719 PMC3794803 source

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    • cites [11] Ferguson RM Khandhar AP Kemp SJ Arami H Saritas EU Croft LR Konkle J Goodwill PW Halkola A Rahmer J Magnetic particle imaging with tailored iron oxide nanoparticle tracers IEEE Trans Med Imaging 2015 34 1077 1084 25438306 PMC4428902 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some approved SPION have later been withdrawn because of the availability of alternative diagnostic probes and protocols.

    “However, some of the approved SPION have later on been withdrawn, because of the availability of alternative diagnostic probes and protocols [27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Wáng YXJ Idée J-M A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging Quant Imaging Med Surg 2017 7 88 122 28275562 PMC5337187 source

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    Premisecitation

    Many iron oxide nanoparticles have been evaluated in preclinical and clinical trials, and several have reached the market.

    “Many iron oxide nanoparticles have been evaluated in preclinical and clinical trials, and several of them have reached the market (Table 1) [4, 22–26].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [4] Jin R Lin B Li D Ai H Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications Curr Opin Pharmacol 2014 18 18 27 25173782 source

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    • cites [22] Qiao R Yang C Gao M Superparamagnetic iron oxide nanoparticles: from preparations to in vivo MRI applications J Mater Chem 2009 19 6274 6293 source

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    • cites [23] Weinstein JS Varallyay CG Dosa E Gahramanov S Hamilton B Rooney WD Muldoon LL Neuwelt EA Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review J Cereb Blood Flow Metab 2010 30 15 35 19756021 PMC2949106 source

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    • cites [24] Xu C Sun S New forms of superparamagnetic nanoparticles for biomedical applications Adv Drug Deliv Rev 2013 65 732 743 23123295 source

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    • cites [25] Laurent S Forge D Port M Roch A Robic C Vander Elst L Muller RN Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications Chem Rev 2008 108 2064 2110 18543879 source

      Not checked in the free run.

    • cites [26] Iv M Telischak N Feng D Holdsworth SJ Yeom KW Daldrup-Link HE Clinical applications of iron oxide nanoparticles for magnetic resonance imaging of brain tumors Nanomedicine 2015 10 993 1018 25867862 source

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    Premisecitation

    SPION have high magnetic moments when exposed to an external magnetic field, and no remaining magnetic moment when the magnetic field is turned off.

    “SPION have high magnetic moments when exposed to an external magnetic field, and no remaining magnetic moment when the magnetic field is turned off [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Gupta AK Naregalkar RR Vaidya VD Gupta M Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications 2007 17716188 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The thickness of the silica shell in sol-gel synthesis is typically tuned by controlling the amount of TEOS and ammonia.

    “The thickness of the silica shell is typically tuned by controlling the amount of TEOS and ammonia [43–45].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [43] Darmawan A Smart S Julbe A Diniz da Costa JC Iron oxide silica derived from sol-gel synthesis Materials 2011 4 448 456 28879999 PMC5448492 source

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    Premisecitation

    While dextran has no direct cytotoxic effects, degradation of the dextran shell may influence certain cellular processes.

    “It has to be kept in mind in this regard that while dextran has no direct cytotoxic effects, the degradation of the dextran shell may influence certain cellular processes [30, 65, 86, 87].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [30] Remya N Syama S Sabareeswaran A Mohanan P Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications Int J Pharm 2016 511 586 598 27451271 source

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    • cites [65] Tassa C Shaw SY Weissleder R Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy Acc Chem Res 2011 44 842 852 21661727 PMC3182289 source

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    • cites [86] Yu M Huang S Yu KJ Clyne AM Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture Int J Mol Sci 2012 13 5554 5570 22754315 PMC3382777 source

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    Premisecitation

    Under hydrothermal conditions, it is difficult to control the final size of particles and most of the time polydisperse samples are obtained.

    “However, it is difficult to control the final size of particles and most of the times polydisperse samples are obtained under hydrothermal conditions [3, 28, 46].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Wu W Wu Z Yu T Jiang C Kim W-S Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications Sci Technol Adv Mater 2015 16 023501 PMC5036481 27877761 source

      Not checked in the free run.

    • cites [28] Hasany S Ahmed I Rajan J Rehman A Systematic review of the preparation techniques of iron oxide magnetic nanoparticles J Nanosci Nanotechnol 2012 2 148 158 source

      Not checked in the free run.

    • cites [46] Wu W He Q Jiang C Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies Nanoscale Res Lett 2008 3 397 21749733 PMC3244954 source

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    Premisecitation

    Among different polymer coatings, PEG and dextran are the most extensively employed, likely because they are generally regarded as safe and are not very rapidly recognized by macrophages in liver and spleen when administered intravenously.

    “Among the different polymer coatings, PEG and dextran are the most extensively employed ones, likely because they are generally regarded as safe (GRAS), and also because they are not very rapidly recognized by macrophages in liver and spleen when administered intravenously [85, 86].”
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    • cites [86] Yu M Huang S Yu KJ Clyne AM Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture Int J Mol Sci 2012 13 5554 5570 22754315 PMC3382777 source

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    Premisecitation

    Prototypic examples of materials used to coat iron oxide nanoparticles are polymers, fatty acids, amino acids, metals, and oxides.

    “Prototypic examples of materials used to coat iron oxide nanoparticles are polymers [28, 47, 50], fatty acids (like oleic acid, stearic acid, lauric acid and dodecylphosphonic acid) [51–55], amino acids (like phenyl alanine, tyrosine, arginine, lysine and cysteine) [56–58],_metals (like gold, gadolinium and silver) [59–61] and oxides (like silica and TiO2) [62–64].”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [28] Hasany S Ahmed I Rajan J Rehman A Systematic review of the preparation techniques of iron oxide magnetic nanoparticles J Nanosci Nanotechnol 2012 2 148 158 source

      Not checked in the free run.

    • cites [47] Sodipo BK Aziz AA One minute synthesis of amino-silane functionalized superparamagnetic iron oxide nanoparticles by sonochemical method Ultrason Sonochem 2018 40 837 840 28946493 source

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    Premisecitation

    Maintenance of micelle structure at high reaction temperature or thermal annealing of synthesized iron oxide are ways to increase the crystallinity of particles prepared by microemulsion.

    “Maintenance of micelle structure at high reaction temperature [41] or thermal annealing of synthesized iron oxide [42] are ways to increase the crystallinity of the particles prepared by this method.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Transmission electron microscopy and atomic force microscopy are powerful techniques to provide information on core size, core size distribution and morphology of iron oxide nanoparticles.

    “Transmission electron microscopy (TEM) and atomic force microscopy (AFM) are powerful techniques to provide information on the core size, core size distribution and morphology of iron oxide nanoparticles [103, 104].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Since electrochemical synthesis reactions are usually performed at room temperature, the synthesized products often show some amorphous parts.

    “Also, since reactions are usually performed at room temperature, the synthesized products often show some amorphous parts [3, 49].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Wu W Wu Z Yu T Jiang C Kim W-S Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications Sci Technol Adv Mater 2015 16 023501 PMC5036481 27877761 source

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    • cites [49] Ramimoghadam D Bagheri S Hamid SBA Progress in electrochemical synthesis of magnetic iron oxide nanoparticles J Magn Magn Mater 2014 368 207 229 source

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    Premisecitation

    r2 typically shows a linear increase with increasing particle core size from 4-5 to 18 nm, while r1 remains rather invariant for particles larger than approximately 8 nm.

    “While r2 typically shows a linear increase with increasing the particle core size from 4-5 to 18 nm, r1 remains rather invariant for particles larger than approximately 8 nm.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
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    Premisecitation

    The liver and spleen typically cope relatively well with high SPION accumulation, which can be explained at least in part by the fact that the liver is the main storage organ for iron in the body.

    “These organs typically cope relatively well with high SPION accumulation, which can be explained – at least in part – by the fact that the liver is main storage organ for iron in the body [132].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Ferucarbotran and ferumoxide have been available on the market and under clinical investigation.

    “Available on the market and under clinical investigation have been ferucarbotran (Resovist®) and ferumoxide (Feridex® (USA), Endorem® (EU); see Table 1 [146, 147].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Studies investigating the toxicity profile of ferumoxytol and ferumoxtran reported less than 1% serious side effects and 10-20% moderate adverse events.

    “Studies investigating the toxicity profile of ferumoxytol and ferumoxtran reported less than 1% of serious side effects (including anaphylatic shock, chest pain, dyspnea and hypotension) and 10-20% of moderate adverse events (such as back pain, headache and urticaria) [135, 136].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    The organic shell surrounding the iron oxide core needs to be stable under physiological conditions and prevent aggregation, as aggregation would result in undesired T2 contrast enhancement.

    “In addition, the organic shell surrounding the core needs to be stable under physiological conditions and it needs to prevent the aggregation of individual nanoparticles, as this would result in an undesired T2 contrast enhancement [141, 142].”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    • cites [142] Hu F Jia Q Li Y Gao M Facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrast T1- and T2-weighted magnetic resonance imaging Nanotechnology 2011 22 245604 21508500 source

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    Premisecitation

    Guardia et al. observed a linear SAR dependence as a function of frequency at a fixed amplitude and a quadratic SAR dependence as a function of amplitude at a fixed frequency for water-soluble iron oxide nanocubes.

    “Interestingly, Guardia et al. observed a linear SAR dependence as a function of frequency (at a fixed amplitude) and a quadratic SAR dependence as a function of amplitude (at a fixed frequency) for water-soluble iron oxide nanocubes [15, 115].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Laurent S Dutz S Häfeli UO Mahmoudi M Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles Adv Colloid Interface Sci 2011 166 8 23 21601820 source

      Not checked in the free run.

    • cites [115] Guardia P Di Corato R Lartigue L Wilhelm C Espinosa A Garcia-Hernandez M Gazeau F Manna L Pellegrino T Water-soluble iron oxide nanocubes with high values of specific absorption rate for cancer cell hyperthermia treatment ACS Nano 2012 6 3080 3091 22494015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Overall, SPION with established coatings such as dextran are generally regarded as safe, while more exotic coatings such as PEI are typically handled with much more caution.

    “Overall, SPION with established coatings such as dextran are generally regarded a safe, while more exotic coatings such as PEI are typically handled with much more caution.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Certain coatings, such as polyethylenimine, have been claimed to show activation of immunological pathways in vitro, as exemplified by M1-like activation of macrophages induced by PEI-coated SPION.

    “Certain coatings, such as polyethylenimine (PEI), have been claimed to show an activation of immunological pathways in vitro, as exemplified e.g. an M1-like activation of macrophages induced by PEI-coated SPION [123, 124].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Xia T Kovochich M Liong M Meng H Kabehie S George S Zink JI Nel AE Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs ACS Nano 2009 3 3273 3286 19739605 PMC3900639 source

      Not checked in the free run.

    • cites [124] Mulens-Arias V Rojas JM Pérez-Yagüe S Morales MP Barber DF Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics Biomaterials 2015 52 494 506 25818455 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In macrophages, ROS regulates cell death, proliferation, motility and phagocytic ability, and it is linked to an M1-like polarisation that helps defend the body against bacteria and other pathogens.

    “In macrophages, ROS regulates cell death, proliferation, motility and phagocytic ability, and it is linked to an M1-like polarisation, which help to defend the body against bacteria and other pathogens [117, 118].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [117] Brüne B Dehne N Grossmann N Jung M Namgaladze D Schmid T von Knethen A Weigert A: Redox control of inflammation in macrophages Antioxidants & redox signaling 2013 19 595 637 23311665 PMC3718318 source

      Not checked in the free run.

    • cites [118] Tan H-Y Wang N Li S Hong M Wang X Feng Y The reactive oxygen species in macrophage polarization: reflecting its dual role in progression and treatment of human diseases Oxid Med Cell Longev 2016 2016 PMC4837277 27143992 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SPION have been extensively used for diagnostic purposes, for visualizing tumors and metastases in liver, spleen and lymph nodes, for angiography as a blood pool agent, and for visualizing inflammatory lesions like atherosclerotic plaques.

    “SPION have been extensively used for diagnostic purposes, for visualizing tumors and metastases in liver, spleen and lymph nodes [137, 138], for angiography as a blood pool agent [139] and for visualizing inflammatory lesions like atherosclerotic plaques [140].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [137] Chen F Ward J Robinson P MR imaging of the liver and spleen: a comparison of the effects on signal intensity of two superparamagnetic iron oxide agents Magn Imaging Reson 1999 17 549 556 10231181 source

      Not checked in the free run.

    • cites [138] Choi J-Y Kim M-J Kim JH Kim SH Ko H-K Lim JS Oh YT Chung J-J Yoo HS Lee JT Detection of hepatic metastasis: manganese-and ferucarbotran-enhanced MR imaging Eur J Radiol 2006 60 84 90 16920315 source

      Not checked in the free run.

    • cites [139] Wang Y-XJ Hussain SM Krestin GP Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging Eur Radiol 2001 11 2319 2331 11702180 source

      Not checked in the free run.

    • cites [140] Neuwelt A Sidhu N Hu C-AA Mlady G Eberhardt SC Sillerud LO Iron-Based Superparamagnetic Nanoparticle Contrast Agents for MRI of Infection and Inflammation Am J Roentgenol 2015 204 W302 W313 25714316 PMC4395032 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In vitro, upon prolonged incubation, surface-coated SPION are typically nontoxic at iron concentrations up to 10 μg/ml, while slight cytotoxicity is seen at 100 μg/ml.

    “In vitro, upon prolonged incubation, surface-coated SPION are typically nontoxic at iron concentration up to and 10 μg/ml, while slight cytotoxicity is seen at 100 μg/ml.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [119] Ankamwar B Lai T-C Huang J-H Liu R-S Hsiao M Chen C-H Hwu Y Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells Nanotechnology 2010 21 075102 20090199 source

      Not checked in the free run.

    • cites [120] Singh N Jenkins GJ Asadi R Doak SH Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION) Nano reviews 2010 1 5358 PMC3215220 22110864 source

      Not checked in the free run.

    • cites [121] Liu G Gao J Ai H Chen X Applications and potential toxicity of magnetic iron oxide nanoparticles Small 2013 9 1533 1545 23019129 source

      Not checked in the free run.

    • cites [122] Mahmoudi M Simchi A Imani M Shokrgozar MA Milani AS Häfeli UO Stroeve P A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles Colloids and Surfaces, B: Biointerfaces 2010 75 300 309 19781921 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gadolinium-based contrast agents show positive contrast enhancement on T1-weighted images, which is clinically generally preferred over negative T2 contrast enhancement mediated by SPION.

    “Gadolinium-based contrast agents show positive contrast enhancement on T1-weighted images, which is clinically generally preferred over negative T2 contrast enhancement mediated for instance by SPION [150].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [150] Matsuo M Kanematsu M Itoh K Murakami T Maetani Y Kondo H Goshima S Kako N Hoshi H Konishi J Moriyama N Detection of Malignant Hepatic Tumors with Ferumoxides-Enhanced, MRI: Comparison of Five Gradient-Recalled Echo Sequences with Different TEs Am J Roentgenol 2004 182 235 242 14684545 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The determined signal intensity for ferucarbotran in the spleen was lower than for ferumoxide, due to overall lower uptake in this organ resulting from the smaller size and lower dose administered for ferucarbotran.

    “In contrast, the determined signal intensity for ferucarbotran in the spleen was lower than for ferumoxide, due to an overall lower uptake in this organ, resulting from the smaller size and lower dose administered for ferucarbotran.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Chen F Ward J Robinson PJ MR imaging of the liver and spleen: a comparison of the effects on signal intensity of two superparamagnetic iron oxide agents Magn Imaging Reson 1999 17 549 556 10231181 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Magnetic particle imaging (MPI) provides 3D information on iron oxide nanoparticle distribution and has advantages over MRI including absence of background signals, high temporal/spatial resolution, high sensitivity, and fast acquisition.

    “Magnetic particle imaging provides 3D information on the distribution of iron oxide nanoparticles, and has several advantages over MRI. These include the absence of potentially disturbing background signals, high temporal and spatial resolution with good quantification features, high sensitivity and fast imaging acquisition [193].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [193] Pablico-Lansigan MH Situ SF Samia ACS Magnetic particle imaging: advancements and perspectives for real-time in vivo monitoring and image-guided therapy Nanoscale 2013 5 4040 4055 23538400 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SPION with a hydrodynamic diameter of 20-30 nm, referred to as ultra-small superparamagnetic iron oxide (USPIO), show a prolonged circulation time and are favorable for lymphography, imaging inflammation and blood pool imaging.

    “SPION with a hydrodynamic diameter of 20-30 nm, which are referred to as ultra-small superparamagnetic iron oxide (USPIO) [154], show a prolonged circulation time and therefore are favorable for lymphography [155], for imaging inflammation [140] and for blood pool imaging [156].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [154] Neuwelt EA Hamilton BE Varallyay CG Rooney WR Edelman RD Jacobs PM Watnick SG Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)? Kidney Int 2009 75 465 474 18843256 PMC2643331 source

      Not checked in the free run.

    • cites [155] Torabi M Aquino SL Harisinghani MG Current Concepts in Lymph Node Imaging J Nucl Med 2004 45 1509 1518 15347718

      Not checked in the free run.

    • cites [140] Neuwelt A Sidhu N Hu C-AA Mlady G Eberhardt SC Sillerud LO Iron-Based Superparamagnetic Nanoparticle Contrast Agents for MRI of Infection and Inflammation Am J Roentgenol 2015 204 W302 W313 25714316 PMC4395032 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The chip-based DMR system was used to quantify shifts in monocyte subtype distribution in inflammatory atherosclerosis in humans, potentially contributing to identification of patients at risk for atherosclerotic plaque rupture.

    “The chip-based DMR system was used for the quantification of shifts in monocyte subtype distribution in inflammatory atherosclerosis in humans, thereby potentially contributing to the identification of patients at risk for atherosclerotic plaque rupture [208].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [208] Wildgruber M Lee H Chudnovskiy A Yoon T-J Etzrodt M Pittet MJ Nahrendorf M Croce K Libby P Weissleder R Swirski FK Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors PLoS One 2009 4 e5663 19461894 PMC2680949 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ferumoxytol does not extravasate into surrounding tissue and allows more reliable rCBV measurements, depicting GBM treatment success more precisely than gadolinium agents.

    “In contrast, ferumoxytol does not extravasate into the surrounding tissue and hence allows more reliable rCBV measurements depicting treatment success of GBM more precisely [191] (Figure 5A).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [191] Gahramanov S Muldoon LL Varallyay CG Li X Kraemer DF Fu R Hamilton BE Rooney WD Neuwelt EA Pseudoprogression of glioblastoma after chemo- and radiation therapy: diagnosis by using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging with ferumoxytol versus gadoteridol and correlation with survival Radiology 2013 266 842 852 23204544 PMC3579176 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MPI is suitable for imaging vascular and cardiac perfusion as well as intervention monitoring in cardiac procedures.

    “MPI is suitable for imaging vascular and cardiac perfusion as well as intervention monitoring in cardiac procedures [195, 196].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [195] Vogel P Rückert MA Klauer P Kullmann WH Jakob PM Behr VC First in vivo traveling wave magnetic particle imaging of a beating mouse heart Phys Med Biol 2016 61 6620 27541258 source

      Not checked in the free run.

    • cites [196] Kratz H Taupitz M Schellenberger AAd Kosch O Eberbeck D Wagner S Trahms L Hamm B Schnorr J Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies PLoS One 2018 13 e0190214 29300729 PMC5754082 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Using MRA instead of CT avoids ionizing radiation exposure, which is beneficial for longitudinal monitoring.

    “An added advantage using MRA instead of CT is that patients are not exposed to ionizing radiation, which is beneficial to perform longitudinal monitoring [183].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] Sakuma H Coronary CT versus MR Angiography: The Role of MR Angiography Radiology 2011 258 340 349 21273518 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    MACS is extensively used in preclinical and clinical cancer research and for sorting white blood cell populations and stem cells.

    “MACS is extensively used in preclinical and clinical cancer research, as well as for sorting white blood cell populations and stem cells [201].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [201] Plouffe BD Murthy SK Lewis LH Fundamentals and Application of Magnetic Particles in Cell Isolation and Enrichment Rep Prog Phys 2015 78 016601 PMC4310825 25471081 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a multicenter clinical trial, contrast-enhanced MR lymphography produced mixed results, arguably due to differences in radiologist experience and expertise.

    “In a multicenter clinical trial, the clinical effectiveness of contrast-enhanced MR lymphography was evaluated, producing mixed results, arguably originating from differences in the experience and expertise of the radiologists involved [162].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [162] Heesakkers RAM Hövels AM Jager GJ van den Bosch HCM Witjes JA Raat HPJ Severens JL Adang EMM van der Kaa CH Fütterer JJ Barentsz J MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study The Lancet Oncology 2008 9 850 856 18708295 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Upon exposure to ultrasound pulses, USPIO-loaded microbubbles are destroyed promoting blood-brain barrier opening; the iron oxide nanoparticles are released from the microbubble shell and extravasate across the permeabilized blood-brain barrier, accumulating in extravascular brain tissue and providing MRI information on the kinetics and extent of blood-brain barrier opening.

    “In this setup, upon exposure to US pulses, USPIO-loaded MB are destroyed promoting BBB opening. During this process, the iron oxide nanoparticles are released from the MB shell and they extravasate across the permeabilized BBB, accumulating in extravascular brain tissue and providing MRI information on the kinetics and the extent of BBB opening (Figure 9A).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The shell of microbubbles can be loaded with iron oxide nanoparticles for image-guided drug delivery purposes.

  • May combine two claims.

    Premisecitation

    Theranostic nanoparticles provide a useful tool to gain knowledge about biodistribution and target site accumulation, and thus help to preselect patients and predict therapy responses.

    “Theranostic nanoparticles provide a useful tool to gain knowledge about biodistribution and target site accumulation, and thus help to preselect patients and predict therapy responses [244].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [244] Lammers T Kiessling F Hennink WE Storm G Nanotheranostics and image-guided drug delivery: current concepts and future directions Mol Pharm 2010 7 1899 1912 20822168 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both MRI and scintigraphy showed similar sensitivity for tracking dendritic cell vaccines, but misadministration could only be detected by MRI.

    “Both methods showed similar sensitivity but misadministration (next to rather than into the lymph node) could only be detected by MRI [126].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] de Vries IJ Lesterhuis WJ Barentsz JO Verdijk P van Krieken JH Boerman OC Oyen WJ Bonenkamp JJ Boezeman JB Adema GJ Bulte JW Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy Nat Biotechnol 2005 23 1407 1413 16258544 source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    SPION treatment of human macrophages pre-polarized to M2-like state causes a shift toward M1 phenotype with increased CD86, TNFα, and intracellular ferritin.

    “As in the above study, they observed a shift in phenotype towards M1, which comes along with an increased expression of CD86, TNFα and intracellular ferritin [213].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [213] Laskar A Eilertsen J Li W Yuan X-M SPION primes THP1 derived M2 macrophages towards M1-like macrophages Biochem Biophys Res Commun 2013 441 737 742 24184477 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Iron oxide-based companion diagnostics can visualize and quantify EPR effect in individual patients and thereby predict therapy responses.

    “Based on the co-localization of nanoparticles applied for imaging (such as SPION) and therapeutic nanoparticles, iron oxide-based companion diagnostics can be applied to visualize and quantify EPR effect in individual patients, and to thereby predict therapy responses.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The EPR effect is highly heterogeneous in cancer, varying between tumor types, patients with the same tumor type, and tumors/metastases in the same patient.
    • Rests on an assumption: Nanoparticles accumulate in tumors via the EPR effect.

  • May combine two claims.

    Interpretationreasoning

    Active targeting strategies do not necessarily increase target site accumulation of nanoparticle formulations because ligand-modified particles are more rapidly recognized by phagocytic cells, reducing circulation times and EPR-mediated tumor accumulation.

    “One has to keep in mind in this regard that active targeting strategies do not necessarily result in increasing the target site accumulation of nanoparticle formulations. More rapid recognition of ligand-modified particles by phagocytic cells in liver, spleen and other organs of the MPS often results in reduced circulation times, and thus in less strong tumor accumulation via the EPR effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Only one magnetically targeted nanocarrier (MTC-DOX) has been evaluated in patients, and it did not produce convincing results, leading to termination of clinical development in phase II/III.

    “From a translational point of view, only one magnetically targeted nanocarrier (which was loaded with doxorubicin; MTC-DOX) has been evaluated in patients, but it did not produce convincing results, leading to termination of clinical development in phase II/III [232, 233].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [232] Wilson MW Kerlan RK Fidelman NA Venook AP LaBerge JM Koda J Gordon RL Hepatocellular Carcinoma: Regional Therapy with a Magnetic Targeted Carrier Bound to Doxorubicin in a Dual MR Imaging/ Conventional Angiography Suite—Initial Experience with Four Patients Radiology 2004 230 287 293 14695402 source

      Not checked in the free run.

    • cites [233] Koda J Venook A Walser E Goodwin S A multicenter, phase I/II trial of hepatic intra-arterial delivery of doxorubicin hydrochloride adsorbed to Magnetic Targeted Carriers in patients with hepatocellular carcinoma Eur Cancer J 2002 38 S18

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Magnetic drug targeting needs very strong magnetic fields for successful application in humans, increasing hardware cost and making it less attractive for clinical implementation.

    “Furthermore, magnetic drug targeting needs very strong magnetic fields for successful application in humans, which increases the cost of the hardware setup, and which makes it less attractive for clinical implementation [199].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [199] Tay ZW Chandrasekharan P Chiu-Lam A Hensley DW Dhavalikar R Zhou XY Yu EY Goodwill PW Zheng B Rinaldi C Conolly SM Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for Arbitrary Localization of Magnetic Hyperthermia Therapy ACS Nano 2018 12 36993713 PMC6007035 29570277 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Medarova et al. achieved substantial silencing of GFP and survivin in tumors using a SPION-based theranostic nanoplatform for siRNA delivery, comparable or superior to previous studies.

    “They achieved substantial silencing (of both GFP and survivin) in tumors, which was comparable or superior to previous published studies. This study thereby provided pioneering proof-of-concept for a SPION-based theranostic nanoplatform for siRNA delivery [239].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [239] Medarova Z Pham W Farrar C Petkova V Moore A In vivo imaging of siRNA delivery and silencing in tumors Nat Med 2007 13 372 17322898 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the same study, when only ferucarbotran was injected into the forebrain, the MPI signal was not detectable for a prolonged period, indicating low retention of ferucarbotran itself in the brain.

    “In case of the former, the MPI signal was not detectable for a prolonged period of time, indicating low retention of ferucarbotran itself in the brain.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [198] Zheng B Vazin T Goodwill PW Conway A Verma A Saritas EU Schaffer D Conolly SM Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast Sci Rep 2015 5 14055 PMC4566119 26358296 source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Mertens et al. were able to precisely localize and sensitively image iron oxide nanoparticle-labeled collagen scaffolds by MRI in mice for up to 22 days.

    “They were able to precisely localize the implants and sensitively image them by MRI (Figure 9D).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [266] Feo DD Merlini A Laterza C Martino G Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection Curr Opin Neurol 2012 25 322 333 22547103 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Al-Jamal et al. concluded that their magnetic drug targeting approach would be feasible in humans if particles of the right size and SPION content can be employed.

    “They concluded that their magnetic drug targeting approach would be feasible in human, if particles of the right size and the right SPION content can be employed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [225] Al-Jamal KT Bai J Wang JT Protti A Southern P Bogart L Heidari H Li X Cakebread A Asker D Al-Jamal WT Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans Nano Lett 2016 16 5652 5660 27541372 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    MSC are capable of differentiating into adipocytes, osteoblasts, chondrocytes, myoblasts and neuron-like cells, making them useful in regenerative medicine.

    “Since MSC are capable of differentiating into a variety of other cells, including adipocytes, osteoblasts, chondrocytes, myoblasts and neuron-like cells, they are highly useful and often employed in regenerative medicine applications [264, 265].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [264] Jasmin n de Souza GT Louzada RA Rosado-de-Castro PH Mendez-Otero R Campos de Carvalho AC Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations Int J Nanomedicine 2017 12 779 793 28182122 PMC5279820 source

      Not checked in the free run.

    • cites [265] Bull E Madani SY Sheth R Seifalian A Green M Seifalian AM Stem cell tracking using iron oxide nanoparticles Int J Nanomedicine 2014 9 1641 1653 24729700 PMC3976208 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Iron oxide nanoparticles are intrinsically suitable for theranostic purposes because they can be visualized by MRI or MPI and their shell can be loaded with therapeutic agents.

    “Iron oxide nanoparticles are intrinsically very suitable for theranostic purposes, because of their ability to be visualized by MRI or MPI, while their shell can be physically or chemically loaded with therapeutic agents.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Iron oxide nanoparticles can be synthesized by multiple different techniques, with co-precipitation, thermal decomposition, microemulsion and sol-gel being the most commonly employed.

    “Iron oxide nanoparticles can be synthesized by multiple different techniques, which all have their own advantages and disadvantages. Co-precipitation, thermal decomposition, microemulsion and sol-gel are the most commonly employed synthetic techniques.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Numerous different preclinical directions are being explored, and more and more clinical applications involve iron oxide nanoparticles.

    “After several initial setbacks, in which ferucarbotran and ferumoxide were initially marketed and later on again withdrawn (because of the availability of better alternatives for the diagnostic applications in question), there are now numerous different preclinical directions that are being explored, and also more and more clinical applications that involve the use of iron oxide nanoparticles.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Magnetic drug targeting and magnetic guidance of devices are extensively explored preclinically, and they may one day find application in a specified sub-set of pathologies.

    “Magnetic drug targeting and magnetic guidance of devices are extensively explored preclinically, and they may one day find application in a specified sub-set of pathologies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    USPIO-labeled vascular graft was visualized and localized with high precision, which was not the case for an unlabeled control vascular graft.

    “As shown in Figure 9E, they were able to visualize and localize the USPIO-labeled graft with high precision, which was not the case for an unlabeled control vascular graft [267].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [267] Saudek F Jirák D Girman P Herynek V Dezortová M Kríz J Peregrin J Berková Z Zacharovova K Hajek M Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans Transplantation 2010 90 1602 1606 21197715

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Surface modification of iron oxide nanoparticles, typically done with polymers, helps to improve biocompatibility, colloidal stability in complex biological environments and in vivo performance.

    “The surface modification of iron oxide nanoparticles, typically done with polymers, helps to improve biocompatibility, colloidal stability in complex biological environments and in vivo performance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Ferumoxtran and ferumoxytol are in clinical trials for imaging lymph node metastasis, especially in prostate cancer.

    “Ferumoxtran and ferumoxytol are in clinical trials for imaging lymph node metastais, especially in prostate cancer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Ferucarbotran and ferumoxide have been employed for visualizing liver tumors and metastases.

    “Ferucarbotran and ferumoxide have been employed for visualizing liver tumors and metastases.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Labeling scaffolds with iron oxide nanoparticles allows for visualization of tissue-engineered implants during and after implantation, for assessing engraftment and degradation, and for longitudinally monitoring functionality and performance.

    “This allows for the visualization of the tissue-engineered implants during and after implantation, for assessing their engraftment and degradation, and for longitudinally monitoring their functionality and performance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Core size, size distribution, crystallinity, shape and saturation magnetization are key parameters that have to be controlled to tailor nanoparticle properties for biomedical applications.

    “Core size, size distribution, crystallinity, shape and saturation magnetization are key parameters that have to be controlled to tailor nanoparticle properties for biomedical applications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Iron oxide nanoparticles in microbubbles can help to obtain valuable information on the efficacy of sonoporation, which holds potential to enhance drug delivery to tumors and to the brain.

    “Iron oxide nanoparticles in microbubbles can help to obtain valuable information on the efficacy of sonoporation, which holds potential to enhance drug delivery to tumors and to the brain.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The shell of microbubbles can be loaded with iron oxide nanoparticles for image-guided drug delivery purposes.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Ferumoxytol has been shown to influence macrophage polarization, which may find future application in multimodal cancer therapy.

    “It has also been shown to influence macrophage polarization, which may find future application in multimodal cancer therapy, for instance to prime the tumor microenvironment for better immunotherapy outcomes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Ferumoxytol has received FDA approval for the treatment of anemia in CKD patients.

    “Ferumoxytol has received FDA approval for the treatment of anemia in CKD patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Depending on core size, iron oxide nanoparticles can be used as either T1-weighted or T2/T2*-weighted MR contrast agents.

    “Depending on their core size, iron oxide nanoparticles can be either used as T1-weighted or T2/T2*-weighted MR contrast agents.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The USPIO-labeled vascular graft showed good biocompatibility and functionality (via time-of-flight angiography) and proper in vivo integration into surrounding tissue, with endogenous blood vessels having formed within the graft.

    “They also showed good biocompatibility and functionality (via time-of-flight angiography) of the graft, and proper in vivo integration into surrounding tissue, with even endogenous blood vessels having formed within the graft.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [267] Saudek F Jirák D Girman P Herynek V Dezortová M Kríz J Peregrin J Berková Z Zacharovova K Hajek M Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans Transplantation 2010 90 1602 1606 21197715

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    NanoThermTM is an iron oxide nanoparticle formulation that is now available on the market for magnetic fluid hyperthermia.

    “NanoTherm™ is an iron oxide nanoparticle formulation that is now available on the market for magnetic fluid hyperthermia.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    In regenerative medicine, iron oxide nanoparticles are often employed in theranostic setups; besides (stem) cell tracking, which has already been done in the clinic, scaffold materials are nowadays routinely labeled with iron oxide nanoparticles.

    “Finally, also in regenerative medicine, iron oxide nanoparticles are often employed in theranostic setups. Besides (stem) cell tracking, which has already been done in the clinic, also scaffold materials are nowadays routinely labeled with iron oxide nanoparticles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Ferumoxtran-based USPIO have been tested for imaging insulitis, and ferumoxytol, ferumoxtran and feruglose have been evaluated as blood pool agents for vascular imaging.

    “Ferumoxtran-based USPIO have been tested for imaging insulitis, and ferumoxytol, ferumoxtran and feruglose have been evaluated as blood pool agent for vascular imaging.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    After initial setbacks, ferucarbotran and ferumoxide were initially marketed and later withdrawn because of availability of better alternatives for the diagnostic applications in question.

    “After several initial setbacks, in which ferucarbotran and ferumoxide were initially marketed and later on again withdrawn (because of the availability of better alternatives for the diagnostic applications in question), there are now numerous different preclinical directions that are being explored, and also more and more clinical applications that involve the use of iron oxide nanoparticles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Ferumoxsil is approved by the FDA as an orally administered contrast agent for gastrointestinal imaging.

    “Ferumoxsil is approved by the FDA as an orally administered contrast agent for gastrointestinal imaging.”
    Quote in the paperNot a substantial claim
67 of 67

  • The paper relies on this without support.

    The magnetic properties of iron oxide nanoparticles depend on their composition and morphology.

    “The magnetic properties of iron oxide nanoparticles depend on their composition and morphology.”

  • The paper relies on this without support.

    Chemical approaches are employed in the vast majority of SPION synthesis cases.

    “Chemical approaches are employed in the vast majority of cases.”

  • The paper relies on this without support.

    Most commercially available SPION are synthesized via co-precipitation.

    “Most of commercially available SPION are synthesized via this method.”

  • The paper relies on this without support.

    Tumor lesions in the liver have lower SPION macrophage uptake than healthy liver parenchyma.

    “Compared to healthy liver tissue, tumor lesions are characterized by lower SPION macrophage uptake as compared to healthy liver parenchyma.”

  • The paper relies on this without support.

    When injected intravenously, USPIO circulate in the bloodstream, extravasate into tissues over time, are cleared by lymphatic vessels, and eventually end up in macrophages inside lymph nodes.

    “When injected intravenously, USPIO circulate in the bloodstream and to some extent extravasate into tissues over time, from where they are cleared by lymphatic vessels, eventually ending up in macrophages inside lymph nodes.”

  • The paper relies on this without support.

    Metastatic manifestation in lymph nodes compromises their function and leads to a decrease in nodal macrophage content.

    “Metastatic manifestation in lymph nodes compromises their function and leads to a decrease in nodal macrophage content.”

  • The paper relies on this without support.

    Due to their superparamagnetic behavior, SPION shorten the relaxation time of surrounding protons.

    “Due to their superparamagnetic behavior, SPION shorten the relaxation time of surrounding protons.”

  • The paper relies on this without support.

    If the core size of SPION is smaller than 4 nm, a shortening of T1 relaxation times can be visualized via T1-weighted MR imaging.

    “If the core size of SPION is smaller than 4 nm, a shortening of T1 relaxation times can be visualized via T1-weighted MR imaging.”

  • The paper relies on this without support.

    The EPR effect is highly heterogeneous in cancer, varying between tumor types, patients with the same tumor type, and tumors/metastases in the same patient.

    “In the last couple of years, it has become increasingly recognized that the EPR effect is a highly heterogeneous phenomenon, especially in cancer. Variability if high between different tumor types, between different patients with the same tumor type, and between different tumors and metastasis in the same patient.”

  • The paper relies on this without support.

    Ferumoxtran-enhanced MR lymphography has not yet been implemented into clinical practice.

    “Even though ferumoxtran-enhanced MR lymphography showed high sensitivity in detection of lymph node metastases, it has not yet been implemented into clinical practice.”

  • The paper relies on this without support.

    MPI does not provide anatomical information.

    “A key disadvantage as compared to MRI is that MPI does not provide anatomical information.”

  • The paper relies on this without support.

    The temperature increase induced by MFH from intravenously administered SPION is generally not sufficiently high for curative cancer therapy due to low local accumulation.

    “The temperature increase induced by magnetic fluid hyperthermia resulting from intravenously administered SPION is generally not sufficiently high to be employed curatively in cancer therapy, due to a too low accumulation of the nanoparticles locally at the tumor site.”

  • The paper relies on this without support.

    Nanoparticles accumulate in tumors via the EPR effect.

    “Nanoparticles accumulate in tumors (and also at sites of inflammation) via the enhanced permeability and retention (EPR) effect.”

  • The paper relies on this without support.

    None of the designed and evaluated actively targeted and magnetic SPION have thus far been translated to the clinic.

    “Even though a variety of promising preclinical data exists and has shown somewhat promising results, none of the designed and evaluated actively targeted and magnetic SPION have thus far been translated to the clinic.”

  • The paper relies on this without support.

    None of the theranostic concepts for regenerative medicine are employed in clinical practice.

    “Thus far, however, none of these theranostic concepts for regenerative medicine are employed in clinical practice.”

  • The paper relies on this without support.

    The real-life situation in cancer patients is much more diverse than that in animal models.

    “The real-life situation in cancer patients is much more diverse than that in animal models.”

  • The paper relies on this without support.

    The shell of microbubbles can be loaded with iron oxide nanoparticles for image-guided drug delivery purposes.

    “The shell of MB can be loaded with iron oxide nanoparticles, for image-guided drug delivery purposes.”
17 of 17

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Iron oxide nanoparticles coated with polymers respond differently to temperature variations and pH gradients, according to a recent study.

    “Iron oxide nanoparticles coated with polymers respond differently to temperature variations and pH gradients, according to a recent study.94,95”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [94]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Collagen-scaffold study is assigned to an unrelated reference

    Minor

    The collagen-scaffold study attributed to Mertens et al. is cited as reference 266, which instead lists Feo et al. and concerns neural stem-cell transplantation.

  • Liu study is attributed to a different author in the cited reference

    Minor

    The text attributes the hydrogel study to Liu et al. and cites reference 264, but reference 264 lists Jasmin et al. and is titled as a review of stem-cell tracking.

  • Citations for clinical cell-labeling studies instead describe scaffolds

    Minor

    The two references cited for clinical studies of labeled neuronal stem cells and pancreatic islet cells are both Mertens et al. papers about labeled scaffold or textile materials.

  • Vascular-graft study is assigned to a pancreatic-islet reference

    Minor

    The account of a USPIO-labeled vascular graft ends with reference 267, but that reference describes MRI of pancreatic islets transplanted into human livers, not vascular grafts in sheep.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Weissleder, 2014, Imaging macrophages with nanoparticles, Nat. Mater., 13, 125, 10.1038/nmat3780 · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Dadfar, S. M., Roemhild, K., Drude, N. I., von Stillfried, S., Knüchel, R., Kiessling, F., & Lammers, T.
Affiliations
  • Universitätsklinikum Aachen (DE)
  • DWI – Leibniz Institute for Interactive Materials (DE)
  • Utrecht University (NL)
Corresponding author
Lammers, Twan
ORCID
Venue
Advanced Drug Delivery Reviews
Publisher
Elsevier BV
Published
2019-01
Volume
138
Pages
302-325
ISSN
0169-409X (ISSN-L)
DOI
10.1016/j.addr.2019.01.005
PMC
PMC7115878
OpenAlex
W2910429314
Cited by
1,181
References
268
Citations by year
2026: 108 · 2025: 161 · 2024: 183 · 2023: 178 · 2022: 206 · 2021: 199 · 2020: 108 · 2019: 38
FWCI
11.11
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Advanced Drug Delivery Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • European Research Council (309495, 680882, 813086)
  • German Research Foundation (La2937/1-2, SFB/TRR57, SFB1066, GRK2375, 331065168)
  • RWTH Aachen University
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
iron oxide nanoparticles, theranostics, magnetic resonance imaging, magnetic particle imaging, iron supplementation, anemia, cancer therapy, macrophage polarization, magnetic hyperthermia, magnetic drug delivery, image-guided drug delivery, blood-brain barrier opening, microbubbles, nanoparticle synthesis, surface functionalization
MeSH terms
Theranostic Nanomedicine, Animals, Ferric Compounds, Humans, Surface Properties, Nanoparticles

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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