Development of Long Circulating Magnetic Particle Imaging Tracers: Use of Novel Magnetic Nanoparticles and Entrapment Into Human Erythrocytes

Antonelli, A.; Szwargulski, Patryk; Scarpa, Emanuele Salvatore; Thieben, Florian; Grüttner, Cordula; Ambrosi, Gianluca; Guidi, Loretta; Ludewig, Peter; Knopp, Tobias; Magnani, Mauro

doi:10.2217/nnm-2019-0449

Cited by 27 publications

(33 citation statements)

References 43 publications

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“…The investigation of RBC-related effects of nanoparticles is actually and continuously relevant as RBCs are studied as potential carriers of USPIONs in the blood to prevent their elimination from the organism and to keep them in a concentration sufficient for the long-term magnetic resonance imaging [29,30]. RBCs are also used to evaluate the efficacy and toxicity of various nanoparticles, mostly under in vitro and ex vivo conditions using hemolytic assay or RBC aggregation [31,32].…”

Section: Discussionmentioning

confidence: 99%

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

et al. 2021

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We determined erythrocyte physiological and biochemical properties after the single and repeated administration of ultra-small superparamagnetic iron-oxide nanoparticles (USPIONs) in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Polyethylene glycol-coated USPIONs (transmission electron microscope detected a mean size of ~30 nm and hydrodynamic size ~51 nm) were intravenously administered to rats either in one infusion at nominal dose 1 mg Fe/kg or in two infusions (administered with a difference of 24 h) at nominal dose 2 mg Fe/kg. Results showed that USPIONs did not deteriorate erythrocyte deformability, nitric oxide production, and osmotic resistance in both experimental settings. Both the single and repeated USPION administration elevated erythrocyte deformability in WKY. However, this effect was not present in SHR; deformability in USPION-treated SHR was significantly lower than in USPION-treated WKY. Nitric oxide production by erythrocytes was increased after a single USPION treatment in WKY, so it can be associated with improvement in erythrocyte deformability. Using biomagnetometry, we revealed significantly lower amounts of USPION-originated iron in erythrocytes in SHR compared with WKY. We found a much faster elimination of USPIONs from erythrocytes in hypertensive rats compared with the normotensive ones, which might be relevant for clinical practice in hypertensive patients undergoing clinical examination with the use of iron-oxide nanoparticles.

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Section: Discussionmentioning

confidence: 99%

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

et al. 2021

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“…Diverse types of NCs were first loaded into RBC ghosts (77). However, the size of the transient pores induced in the RBC membrane using standard osmotic swelling does not exceed 50 nm (78). Smuggling larger particles requires more invasive and damaging RBC approaches.…”

Section: Nanoparticles Hitchhiking On Rbcs: Transformative Changes In Pharmacokinetics and Biodistribution Vascular Transfer And Potentiamentioning

confidence: 99%

Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers

Brenner

Mitragotri

Muzykantov

2021

Annu. Rev. Biomed. Eng.

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Red blood cell (RBC) hitchhiking is a method of drug delivery that can increase drug concentration in target organs by orders of magnitude. In RBC hitchhiking, drug-loaded nanoparticles (NPs) are adsorbed onto red blood cells and then injected intravascularly, which causes the NPs to transfer to cells of the capillaries in the downstream organ. RBC hitchhiking has been demonstrated in multiple species and multiple organs. For example, RBC-hitchhiking NPs localized at unprecedented levels in the brain when using intra-arterial catheters, such as those in place immediately after mechanical thrombectomy for acute ischemic stroke. RBC hitchhiking has been successfully employed in numerous preclinical models of disease, ranging from pulmonary embolism to cancer metastasis. In addition to summarizing the versatility of RBC hitchhiking, we also describe studies into the surprisingly complex mechanisms of RBC hitchhiking as well as outline future studies to further improve RBC hitchhiking's clinical utility. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…This was briefly investigated by encapsulating commercial polymer coated iron oxide particles into red blood cells. [20] The obtained MPS signals of the cells with the tracers revealed a strong discrepancy to the reference samples in water. Such differences between effective and predicted tracer concentrations are highly problematic.…”

Section: Introductionmentioning

confidence: 89%

Particle interactions and their effect on magnetic particle imaging and spectroscopy

Moor

Scheibler

Gerken

et al. 2021

Preprint

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Tracer and thus signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared and characterized Zn0.4Fe2.6O4 nanoparticles and controlled their interparticle distance by variying SiO2 coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller interparticle distance. The SiO2-coated Zn0.4Fe2.6O4 outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO2-coated Zn-ferrites against commercially available PVP-coated Fe3O4 nanoparticles in water and PBS. PBS is known to destabilize nanoparticles mimicking an agglomeration in vivo. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their aggregated morphology formed during their flame-synthesis. On the other hand, the MPS signal of commercial PVP-coated Fe3O4 strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a mammalian cell model. For PVP-coated Fe3O4, we could detect a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO2-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe3O4 could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of MPI using such standard commercial tracers and highlights the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.

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Development of Long Circulating Magnetic Particle Imaging Tracers: Use of Novel Magnetic Nanoparticles and Entrapment Into Human Erythrocytes

Cited by 27 publications

References 43 publications

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers

Particle interactions and their effect on magnetic particle imaging and spectroscopy

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