Effect of Ligand Structure on MnO Nanoparticles for Enhanced <i>T</i><sub>1</sub> Magnetic Resonance Imaging of Inflammatory Macrophages

Park, Joseph; Bang, Doyeon; Kim, Eunjung; Yang, Jaemoon; Lim, Eun‐Kyung; Choi, Jihye; Kang, Byunghoon; Park, Hyo Seon; Huh, Yong Min; Haam, Seungjoo

doi:10.1002/ejic.201201026

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…Indeed, MnO particles of similar size (7-8 nm core diameter) coated with DMSA-PEG or carboxymethyldextran have relaxometric ratios in the same order as MnO@PDns (r 2 /r 1 $ 4; r 1 ¼ 3.4 mM À1 s À1 for DMSA-PEG, and r 2 /r 1 ¼ 5.3; r 1 ¼ 5.4 mM À1 s À1 for carboxymethyldextran, both measured at 1.5 Tesla). 11,18 As a comparison, the expected relaxivities for Mn 2+ ions measured at 1.41 Tesla and 25 C are r 1 ¼ 5.2 mM À1 s À1 and r 2 ¼ 61 mM À1 s À1 . 35 Therefore, the relaxometric ratios measured for MnO@PDns are more favorable to T 1 -weighted imaging compared to that of Mn 2+ ions only (r 2 /r 1 $ 10 at 1.41 T).…”

Section: Relaxometric Analysis and In Vitro Mri Performancementioning

confidence: 99%

“…[4][5][6][7][8][9][10]12,[14][15][16][17] In fact, small nanoparticles showing high atomic surface ratios induce stronger positive contrast enhancement in MRI. 18 These particles, stable in saline suspensions, are coated with biocompatible and hydrophilic molecules (e.g. PEG, D-glucuronic, and dextran).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, aqueous Mn 2+ solutions show relaxivities in the order of r 1 ¼ 5.2 mM À1 s À1 and r 2 ¼ 61 mM À1 s À1 at 1.41 Tesla and 25 C. 35 Hence, different coating strategies were recently adopted to provide enhanced colloidal stability, with possible improvement on the chemical stability of nanoparticles. 10,18 Unfortunately, no clear demonstration of enhanced chemical stability was performed aer the coating of MnO particles with carboxymethyldextran and polyethylene sulfonate molecules. An optimal polymeric ligand that could prevent nanoparticle core degradation, while preserving relaxometric properties and colloidal stability, is still to be developed.…”

Section: Introductionmentioning

confidence: 99%

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Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

et al. 2014

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A majority of MRI procedures requiring intravascular injections of contrast agents are performed with paramagnetic chelates. Such products induce vascular signal enhancement and they are rapidly excreted by the kidneys. Unfortunately, each chelate is made of only one paramagnetic ion, which, taken individually, has a limited impact on the MRI signal. In fact, the detection of molecular events in the nanomolar range using T 1 -weighted MRI sequences requires the design of ultra-small particles containing hundreds of paramagnetic ions per contrast agent unit. Ultra-small nanoparticles of manganese oxide (MnO, 6-8 nm diameter) have been developed and proposed as an efficient and at least 1000Â more sensitive "positive" MRI contrast agent. However no evidence has been found until now that an adequate surface treatment of these particles could maintain their strong blood signal enhancement, while allowing their rapid and efficient excretion by the kidneys or by the hepatobiliairy pathway. Indeed, the sequestration of MnO particles by the reticuloendothelial system followed by strong uptake in the liver and in the spleen could potentially lead to Mn 2+ -induced toxicity effects. For ultra-small MnO particles to be applied in the clinics, it is necessary to develop coatings that also enable their efficient excretion within hours. This study demonstrates for the first time the possibility to use MnO particles as T 1 vascular contrast agents, while enabling the excretion of >70% of all the Mn injected doses after 48 h. For this, small, biocompatible and highly hydrophilic pegylated bis-phosphonate dendrons (PDns) were grafted on MnO particles to confer colloidal stability, relaxometric performance, and fast excretion capacity. The chemical and colloidal stability of MnO@PDn particles were confirmed by XPS, FTIR and DLS. The relaxometric performance of MnO@PDns as "positive" MRI contrast agents was assessed (r 1 ¼ 4.4 mM À1 s À1 , r 2 /r 1 ¼ 8.6; 1.41 T and 37 C). Mice were injected with 1.21 mg Mn per kg (22 mmol Mn per kg), and scanned in MRI up to 48 h.The concentration of Mn in key organs was precisely measured by neutron activation analysis and confirmed, with MRI, the possibility to avoid RES nanoparticle sequestration through the use of phosphonate dendrons. Due to the fast kidney and hepatobiliairy clearance of MnO particles conferred by PDns, MnO nanoparticles can now be considered for promising applications in T 1 -weighted MRI applications requiring less toxic although highly sensitive "positive" molecular contrast agents.

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Section: Relaxometric Analysis and In Vitro Mri Performancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

et al. 2014

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“…1 Additionally, some Gd-loaded nanoparticles with poor stability may release individual Gd ions, which can cause biological toxicity after they are absorbed by the gastrointestinal tract in vivo. 2,[9][10][11] Therefore, it is necessary to identify ideal Gdchelators with good biocompatibility, stability, and sensitivity for cell tracking.…”

Section: Introductionmentioning

confidence: 99%

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin‐based gadolinium³⁺ nanoparticles

Cai

Wang

et al. 2016

J Biomedical Materials Res

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Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we designed and synthesized melanin-based gadolinium (Gd )-chelate nanoparticles (MNP-Gd ) of ∼7 nm for stem cell tracking in vivo. MNP-Gd possesses many beneficial properties, such as its high stability and sensitivity, shorter T1 relaxation time, higher cell labeling efficiency, and lower cytotoxicity compared with commercial imaging agents. We found that the T1 relaxivity (r ) of MNP-Gd was significantly higher than that of Gd-DTPA; the nanoparticles were taken up by bone mesenchymal stem cells (BMSCs) via endocytosis and were broadly distributed in the cytoplasm. Based on an in vitro MTT assay, no cytotoxicity of labeled stem cells was observed for MNP-Gd concentrations of less than 800 µg/mL. Furthermore, we tracked MNP-Gd -labeled BMSCs in vivo using 3.0T MRI equipment. After intramuscular injection, MNP-Gd -labeled BMSCs were detected, even after four weeks, by 3T MRI. We concluded that MNP-Gd nanoparticles at appropriate concentrations can be used to effectively monitor and track BMSCs in vivo. MNP-Gd nanoparticles have potential as a new positive MRI contrast agent in clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 131-137, 2017.

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“…g-Fe 2 O 3 ), have been described as T 1 -based CAs. 45,46 The T 1 -based CAs enhance the relaxation of water in two pathways. Firstly the inner-sphere water which binds directly to the metal ion relaxes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of nanoparticles, their biocompatibility, and toxicity behavior for biomedical applications

Gautam

Veggel

2013

J. Mater. Chem. B

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Nanomaterials research has in part been focused on their use in biomedical applications for more than several decades. However, in recent years this field has been developing to a much more advanced stage by carefully controlling the size, shape, and surface-modification of nanoparticles. This review provides an overview of two classes of nanoparticles, namely iron oxide and NaLnF 4 , and synthesis methods, characterization techniques, study of biocompatibility, toxicity behavior, and applications of iron oxide nanoparticles and NaLnF 4 nanoparticles as contrast agents in magnetic resonance imaging.Their optical properties will only briefly be mentioned. Iron oxide nanoparticles show a saturation of magnetization at low field, therefore, the focus will be MLnF 4 (Ln ¼ Dy 3+ , Ho 3+ , and Gd 3+ ) paramagnetic nanoparticles as alternative contrast agents which can sustain their magnetization at high field. The reason is that more potent contrast agents are needed at magnetic fields higher than 7 T, where most animal MRI is being done these days. Furthermore we observe that the extent of cytotoxicity is not fully understood at present, in part because it is dependent on the size, capping materials, dose of nanoparticles, and surface chemistry, and thus needs optimization of the multidimensional phenomenon. Therefore, it needs further careful investigation before being used in clinical applications.

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Effect of Ligand Structure on MnO Nanoparticles for Enhanced T₁ Magnetic Resonance Imaging of Inflammatory Macrophages

Cited by 15 publications

References 27 publications

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin‐based gadolinium³⁺ nanoparticles

Synthesis of nanoparticles, their biocompatibility, and toxicity behavior for biomedical applications

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Effect of Ligand Structure on MnO Nanoparticles for Enhanced T1 Magnetic Resonance Imaging of Inflammatory Macrophages

Cited by 15 publications

References 27 publications

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

Tailored biological retention and efficient clearance of pegylated ultra-small MnO nanoparticles as positive MRI contrast agents for molecular imaging

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin‐based gadolinium3+ nanoparticles

Synthesis of nanoparticles, their biocompatibility, and toxicity behavior for biomedical applications

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Product

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Effect of Ligand Structure on MnO Nanoparticles for Enhanced T₁ Magnetic Resonance Imaging of Inflammatory Macrophages

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin‐based gadolinium³⁺ nanoparticles