Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications

Friedrich, Bernhard; Lyer, Stefan; Janko, Christina; Unterweger, Harald; Brox, Regine; Cunningham, Sarah; Dutz, Silvio; Taccardi, Nicola; Bikker, Floris J.; Hurle, Katrin; Sebald, Heidi; Lenz, Malte; Spiecker, Erdmann; Fester, Lars; Hackstein, Holger; Strauß, Richard; Boccaccını, Aldo R.; Bogdan, Christian; Tietze, Rainer

doi:10.1016/j.actbio.2022.01.001

Cited by 14 publications

(44 citation statements)

References 47 publications

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“…To evaluate the endotoxin level of the nanoparticles, the EndoZyme recombinant factor C assay was used [ 31 ]. As shown in Figure 2 C, the detected endotoxin amounts were 0.010 EU/mL for SPION Dex30 and 0.015 EU/mL for SPION Dex80 (both at an iron concentration of 25 µg/mL).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the presence of the particles at the given concentrations seemed to have neither induced, nor reduced the growth of bacteria on agar plates by visual examination (Figure 2B). To evaluate the endotoxin level of the nanoparticles, the EndoZyme recombinant factor C assay was used [31]. As shown in Figure 2C, the detected endotoxin amounts were 0.010 EU/mL for SPION Dex30 and 0.015 EU/mL for SPION Dex80 (both at an iron concentration of 25 µg/mL).…”

Section: Sterility and Endotoxin Contentmentioning

confidence: 99%

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Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes

et al. 2022

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Dextran-coated superparamagnetic iron oxide nanoparticles (SPIONDex) of various sizes can be used as contrast agents in magnetic resonance imaging (MRI) of different tissues, e.g., liver or atherosclerotic plaques, after intravenous injection. In previous studies, the blood compatibility and the absence of immunogenicity of SPIONDex was demonstrated. The investigation of the interference of SPIONDex with stimulated immune cell activation is the aim of this study. For this purpose, sterile and endotoxin-free SPIONDex with different hydrodynamic sizes (30 and 80 nm) were investigated for their effect on monocytes, dendritic cells (DC) and lymphocytes in concentrations up to 200 µg/mL, which would be administered for use as an imaging agent. The cells were analyzed using flow cytometry and brightfield microscopy. We found that SPIONDex were hardly taken up by THP-1 monocytes and did not reduce cell viability. In the presence of SPIONDex, the phagocytosis of zymosan and E. coli by THP-1 was dose-dependently reduced. SPIONDex neither induced the maturation of DCs nor interfered with their stimulated maturation. The particles did not induce lymphocyte proliferation or interfere with lymphocyte proliferation after stimulation. Since SPIONDex rapidly distribute via the blood circulation in vivo, high concentrations were only reached locally at the injection site immediately after application and only for a very limited time. Thus, SPIONDex can be considered immune compatible in doses required for use as an MRI contrast agent.

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Section: Resultsmentioning

confidence: 99%

Section: Sterility and Endotoxin Contentmentioning

confidence: 99%

Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes

et al. 2022

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“…This study uses SPIONs ( Figure 1 a) that are coated with APTES, a surface coating that provides vast possibilities for attachment of different molecules through free amino groups ( Figure 1 b,c). The SPIONs were produced using a one-step coprecipitation process [ 8 , 32 , 33 ]. Briefly, Iron(II) chloride and iron(III) chloride were dissolved in water in a molar ratio of 1:2.…”

Section: Methodsmentioning

confidence: 99%

“…SPIONs are being investigated and used for a plethora of different applications, including the delivery of siRNA in gene therapy, the targeted delivery of chemotherapeutics, induction of apoptosis in cancer cells through magnetic hyperthermia, and as an MRI contrast agent [ 1 , 2 , 3 , 4 , 5 ]. SPIONs coated with (3-Aminopropyle)-Triethoxysilane (SPION-APTES), due to the free amino groups on their surface, offer the possibility to link various therapeutic agents and substances for different medical applications [ 6 , 7 , 8 ]. These characteristics make them a prime candidate for many applications but particularly for new approaches in tumor therapy, where they have already been studied for the targeted application of chemotherapeutics, growth-inhibitors, or antibodies on cancers such as cervical carcinoma, lymphoma, and ovarian cancer [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

et al. 2023

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Superparamagnetic iron nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics. Therefore, we investigated SPIONs coated with (3-Aminopropyle)-Triethoxysilane (SPION-APTES) for their influence on different head and neck squamous cell carcinoma (HNSCC) cell lines, as well as for their suitability as a radiosensitizer. We used 24-well microscopy and immunofluorescence microscopy for cell observation, growth curves to determine cytostatic effects, and colony formation assays to determine cytotoxicity. We found that the APTES-SPIONs were very well taken up by the HNSCC cells. They generally have a low cytotoxic effect, showing no significant difference in clonogenic survival between the control group and cells treated with 20 µg Fe/mL (p > 0.25) for all cell lines. They have a cytostatic effect on some cell lines cells (e.g., Cal33) that is visible across different radiation doses (1, 2, 8 Gy, p = 0.05). In Cal33, e.g., SPION-APTES raised the doubling time at 2 Gy from 24.53 h to 41.64 h. Importantly, these findings vary notably between the cell lines. However, they do not significantly alter the radiation effect: only one out of eight cell lines treated with SPION-APTES showed a significantly reduced clonogenic survival after ionizing radiation with 2 Gy, and only two showed significantly reduced doubling times. Thus, although the APTES-SPIONs do not qualify as a radiosensitizer, we were still able to vividly demonstrate and analyze the effect that the APTES-SPIONs have on various cell lines as a contribution to further functionalization.

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“…They are coated with APTES and produced by alkaline precipitation (Supplementary Fig. 5 ) 25 . The MNPs produced in this way have a hydrodynamic diameter of about 200 nm with the single crystallites showing a diameter of about 12 nm.…”

Section: Methodsmentioning

confidence: 99%

Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics

et al. 2022

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Magnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity.

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Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications

Cited by 14 publications

References 47 publications

Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes

Biocompatibility of Dextran-Coated 30 nm and 80 nm Sized SPIONs towards Monocytes, Dendritic Cells and Lymphocytes

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics

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