Simulation of the Long-Term Fate of Superparamagnetic Iron Oxide-Based Nanoparticles Using Simulated Biological Fluids

Rabel, Martin; Warncke, Paul; Grüttner, Cordula; Bergemann, Christian; Kurland, Heinz-Dieter; Müller, Robert N.; Dugandžić, Vera; Thamm, Jana; Müller, Frank A.; Popp, Jürgen; Cialla‐May, Dana; Fischer, Dagmar

doi:10.2217/nnm-2018-0382

Cited by 19 publications

(33 citation statements)

References 68 publications

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“…10,11 Studies of the long-term fate of the iron oxide nanoparticles in the body are still very limited. A few studies are devoted to in vitro degradation in simulated lysosomal conditions, 12,13 cell cultures, 14,15 and spheroids. 16 These studies showed some aspects of biotransformation of the magnetic particles, including a release of metal ions, involvement of the iron metabolic protein complex in iron scavenging, gradual transition of the particles to the form of ferritin, and a possibility of de novo particle synthesis from the degradation products.…”

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confidence: 99%

Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study

et al. 2021

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Safe application of nanoparticles in medicine requires full understanding of their pharmacokinetics including catabolism in the organism. However, information about nanoparticle degradation is still scanty due to difficulty of long-term measurements by invasive techniques. Here, we describe a magnetic spectral approach for in vivo monitoring of magnetic particle (MP) degradation. The method noninvasiveness has allowed performing of a broad comprehensive study of the 1-year fate of 17 types of iron oxide particles. We show a long-lasting influence of five parameters on the MP degradation half-life: dose, hydrodynamic size, ζ-potential, surface coating, and internal architecture. We observed a slowdown in MP biotransformation with an increase of the injected dose and faster degradation of the particles of a small hydrodynamic size. A comparison of six types of 100 nm particles coated by different hydrophilic polymer shells has shown that the slowest (t 1/2 = 38 ± 6 days) and the fastest (t 1/2 = 15 ± 4 days) degradations were achieved with a polyethylene glycol and polyglucuronic acid coatings, respectively. The most significant influence on the MP degradation was due to the internal architecture of the particles as the coverage of magnetic cores with a solid 39 nm polystyrene layer slowed down the half-life of the core−shell MPs from 48 days to more than 1 year. The revealed deeper insights into the particle degradation in vivo may facilitate rational design of nano-and microparticles with predictable long-term fate in vivo.

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confidence: 99%

Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study

et al. 2021

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“…In these models, the authors deomstrated that metallic ions can be released due to the acidic pH of lysosomes after the uptake, exerting their action through an interaction with the thiol and selenol groups of the TrxR enzyme. Therefore, IONP degradation kinetic profiles were determined in ALF for both kinds of nanoparticles according to a procedure previously described [ 34 ] ( Figure S12 ). It is interesting to note that most of the nanoparticles were digested after 48 h of incubation.…”

Section: Resultsmentioning

confidence: 99%

“…ALF and BLF were prepared according to Rabel et al [ 34 ]. After membrane filtration (membrane cut-off: 14 kDa), the sterilized fluids were stored at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles’ Radiosensitizing Properties

et al. 2023

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Among the plethora of nanosystems used in the field of theranostics, iron oxide nanoparticles (IONPs) occupy a central place because of their biocompatibility and magnetic properties. In this study, we highlight the radiosensitizing effect of two IONPs formulations (namely 7 nm carboxylated IONPs and PEG5000-IONPs) on A549 lung carcinoma cells when exposed to 225 kV X-rays after 6 h, 24 h and 48 h incubation. The hypothesis that nanoparticles exhibit their radiosensitizing effect by weakening cells through the inhibition of detoxification enzymes was evidenced by thioredoxin reductase activity monitoring. In particular, a good correlation between the amplification effect at 2 Gy and the residual activity of thioredoxin reductase was observed, which is consistent with previous observations made for gold nanoparticles (NPs). This emphasizes that NP-induced radiosensitization does not result solely from physical phenomena but also results from biological events.

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“…To better understand the impact of coating materials on the IONs degradation and agglomeration profile, BIONs, ION@Dex, ION@PVA, and ION@PLGA were incubated in SBF, ALF, AEF, and PBS for 72 hours at 37 °C (Figure 4). In contrast to Rabel et al, a faster protocol was used here, which shortens the protocol to three days (vs. 28 days) [36]. Faster shaking speeds (1000 rpm vs 110 rpm) ensure that the particles are kept in suspension and therefore have more contact with the medium.…”

Section: Agglomeration and Fe 2+ -Release Studymentioning

confidence: 99%

Screening of superparamagnetic iron oxide nanoparticles for their application in the human body: Influence of various coatings

Turrina

Klassen

Milani

et al. 2023

Preprint

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Iron oxide nanoparticles (IONs) are of great interest in nanomedicine for imaging, drug delivery, or for hyperthermia treatment. Although many research groups have focused on the synthesis and application of IONs in nanomedicine, little is known about the influence of the surface properties on the particles’ behavior in the human body. This study analyzed the impact of standard coating materials (dextran, polyvinyl alcohol, polylactide-co-glycolide) with an improved experimental setting on the IONs’ cytocompatibility, degradation, and agglomeration profile and their oxidative stress. All particles, including bare IONs (BIONs), showed good cytocompatibility (>70%) with smooth muscle cells. The polyvinyl alcohol coating led to the least agglomeration over a pH range from 4 to 10 in water. Small-angle X-ray scattering profiles could visualize aggregation and primary particle sizes around 20 nm for BIONs and dextran-coated IONs. A combined experimental setup of dynamic light scattering and phenanthroline assay was used to analyze the long-term agglomeration and degradation profile of IONs in simulated body fluids, allowing fast screening of multiple candidates. All particles degraded in simulated endosomal and lysosomal fluid, confirming the pH-dependent dissolution. The degradation rate decreased with the shrinking size of particles leading to a plateau. The fastest Fe2+ release could be measured for the polyvinyl-coated IONs. The analytical setup is ideal for a quick preclinical study of IONs, giving often neglected yet crucial information about the behavior and toxicity of nanoparticles in the human body.

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Simulation of the Long-Term Fate of Superparamagnetic Iron Oxide-Based Nanoparticles Using Simulated Biological Fluids

Cited by 19 publications

References 68 publications

Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study

Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles’ Radiosensitizing Properties

Screening of superparamagnetic iron oxide nanoparticles for their application in the human body: Influence of various coatings

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