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Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.

Starmans LW, Moonen RP, Aussems-Custers E, Daemen MJ, Strijkers GJ, Nicolay K, Grüll H - PLoS ONE (2015)

Bottom Line: ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01).Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles.The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

ABSTRACT
Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.

No MeSH data available.


Related in: MedlinePlus

FibPep-ION-Micelle nanoplatform.(A) Schematic representation of the FibPep-ION-Micelle nanoplatform. Reproduced from Starmans and coworkers [10]. (B) Volume-weighted size-distribution profiles of the FibPep-ION-Micelles and NCFibPep-ION-Micelles at the day of synthesis (D0) and at the final day of the in vivo experiments (13 days post synthesis, D13). (C, D) Representative cryo-TEM images of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles.
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pone.0119257.g001: FibPep-ION-Micelle nanoplatform.(A) Schematic representation of the FibPep-ION-Micelle nanoplatform. Reproduced from Starmans and coworkers [10]. (B) Volume-weighted size-distribution profiles of the FibPep-ION-Micelles and NCFibPep-ION-Micelles at the day of synthesis (D0) and at the final day of the in vivo experiments (13 days post synthesis, D13). (C, D) Representative cryo-TEM images of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles.

Mentions: Fibrin-targeted FibPep-ION-Micelles (Fig. 1A) and non-fibrin-specific NCFibPep-ION-Micelles were synthesized according to a previously published protocol [10]. The dispersion state of the synthesized nanoparticles in HEPES buffered saline (HBS, pH 7.4) was investigated using dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) measurements. Immediately after synthesis of the nanoparticles, one peak was observed with a maximum intensity at a hydrodynamic diameter of 40 nm (Fig. 1B). At the conclusion of the in vivo experiments (13 days post-synthesis), DLS was performed once more, and showed identical results for both FibPep-ION-Micelles and NCFibPep-ION-Micelles, indicating excellent intrinsic stability of the particles over the time course of the study. Cryo-TEM analysis showed that FibPep-ION-Micelles and NCFibPep-ION-Micelles were dispersed in HBS as single particles or as small aggregates of nanoparticles (Fig. 1C-D). FibPep-ION-Micelles and NCFibPep-ION-Micelles displayed a longitudinal relaxivity of 5.6 and 5.4 mM-1s-1 and a transversal relaxivity of 207 and 204 mM-1s-1, respectively and are thus well suited to allow sensitive detection by T2-weighted MR imaging. MPS was performed to assess the capacity of the (NC)FibPep-ION-Micelles to induce a signal for MPI purposes. Resovist was measured as a reference. FibPep-ION-Micelles induced similar MPS signal in comparison to NCFibPep-ION-Micelles (Fig. 2). The signal of (NC)FibPep-ION-Micelles was up to 750 times increased with respect to Resovist, indicating that the (NC)FibPep-ION-Micelles are potent contrast agents for MPI.


Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.

Starmans LW, Moonen RP, Aussems-Custers E, Daemen MJ, Strijkers GJ, Nicolay K, Grüll H - PLoS ONE (2015)

FibPep-ION-Micelle nanoplatform.(A) Schematic representation of the FibPep-ION-Micelle nanoplatform. Reproduced from Starmans and coworkers [10]. (B) Volume-weighted size-distribution profiles of the FibPep-ION-Micelles and NCFibPep-ION-Micelles at the day of synthesis (D0) and at the final day of the in vivo experiments (13 days post synthesis, D13). (C, D) Representative cryo-TEM images of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352001&req=5

pone.0119257.g001: FibPep-ION-Micelle nanoplatform.(A) Schematic representation of the FibPep-ION-Micelle nanoplatform. Reproduced from Starmans and coworkers [10]. (B) Volume-weighted size-distribution profiles of the FibPep-ION-Micelles and NCFibPep-ION-Micelles at the day of synthesis (D0) and at the final day of the in vivo experiments (13 days post synthesis, D13). (C, D) Representative cryo-TEM images of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles.
Mentions: Fibrin-targeted FibPep-ION-Micelles (Fig. 1A) and non-fibrin-specific NCFibPep-ION-Micelles were synthesized according to a previously published protocol [10]. The dispersion state of the synthesized nanoparticles in HEPES buffered saline (HBS, pH 7.4) was investigated using dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) measurements. Immediately after synthesis of the nanoparticles, one peak was observed with a maximum intensity at a hydrodynamic diameter of 40 nm (Fig. 1B). At the conclusion of the in vivo experiments (13 days post-synthesis), DLS was performed once more, and showed identical results for both FibPep-ION-Micelles and NCFibPep-ION-Micelles, indicating excellent intrinsic stability of the particles over the time course of the study. Cryo-TEM analysis showed that FibPep-ION-Micelles and NCFibPep-ION-Micelles were dispersed in HBS as single particles or as small aggregates of nanoparticles (Fig. 1C-D). FibPep-ION-Micelles and NCFibPep-ION-Micelles displayed a longitudinal relaxivity of 5.6 and 5.4 mM-1s-1 and a transversal relaxivity of 207 and 204 mM-1s-1, respectively and are thus well suited to allow sensitive detection by T2-weighted MR imaging. MPS was performed to assess the capacity of the (NC)FibPep-ION-Micelles to induce a signal for MPI purposes. Resovist was measured as a reference. FibPep-ION-Micelles induced similar MPS signal in comparison to NCFibPep-ION-Micelles (Fig. 2). The signal of (NC)FibPep-ION-Micelles was up to 750 times increased with respect to Resovist, indicating that the (NC)FibPep-ION-Micelles are potent contrast agents for MPI.

Bottom Line: ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01).Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles.The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

ABSTRACT
Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.

No MeSH data available.


Related in: MedlinePlus