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16 pages, 7764 KiB

Open AccessArticle

Magnetically Assisted Control of Stem Cells Applied in 2D, 3D and In Situ Models of Cell Migration

by Richard Harrison, Jeni Luckett, Sarah Marsh, Hilda Anaid Lugo Leija, Shelanah Salih, Reem Alkharji and Virginie Sottile

Molecules 2019, 24(8), 1563; https://doi.org/10.3390/molecules24081563 - 19 Apr 2019

Cited by 4 | Viewed by 3134

Abstract

The success of cell therapy approaches is greatly dependent on the ability to precisely deliver and monitor transplanted stem cell grafts at treated sites. Iron oxide particles, traditionally used in vivo for magnetic resonance imaging (MRI), have been shown to also represent a [...] Read more.

The success of cell therapy approaches is greatly dependent on the ability to precisely deliver and monitor transplanted stem cell grafts at treated sites. Iron oxide particles, traditionally used in vivo for magnetic resonance imaging (MRI), have been shown to also represent a safe and efficient in vitro labelling agent for mesenchymal stem cells (MSCs). Here, stem cells were labelled with magnetic particles, and their resulting response to magnetic forces was studied using 2D and 3D models. Labelled cells exhibited magnetic responsiveness, which promoted localised retention and patterned cell seeding when exposed to magnet arrangements in vitro. Directed migration was observed in 2D culture when adherent cells were exposed to a magnetic field, and also when cells were seeded into a 3D gel. Finally, a model of cell injection into the rodent leg was used to test the enhanced localised retention of labelled stem cells when applying magnetic forces, using whole body imaging to confirm the potential use of magnetic particles in strategies seeking to better control cell distribution for in vivo cell delivery. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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17 pages, 4610 KiB

Open AccessArticle

The Effect of Rhodamine-Derived Superparamagnetic Maghemite Nanoparticles on the Motility of Human Mesenchymal Stem Cells and Mouse Embryonic Fibroblast Cells

by Larisa Baiazitova, Josef Skopalik, Jiri Chmelik, Inna Zumberg, Vratislav Cmiel, Katerina Polakova and Ivo Provaznik

Molecules 2019, 24(7), 1192; https://doi.org/10.3390/molecules24071192 - 27 Mar 2019

Cited by 2 | Viewed by 3267

Abstract

Nanoparticles have become popular in life sciences in the last few years. They have been produced in many variants and have recently been used in both biological experiments and in clinical applications. Due to concerns over nanomaterial risks, there has been a dramatic [...] Read more.

Nanoparticles have become popular in life sciences in the last few years. They have been produced in many variants and have recently been used in both biological experiments and in clinical applications. Due to concerns over nanomaterial risks, there has been a dramatic increase in investigations focused on safety research. The aim of this paper is to present the advanced testing of rhodamine-derived superparamagnetic maghemite nanoparticles (SAMN-R), which are used for their nontoxicity, biocompatibility, biodegradability, and magnetic properties. Recent results were expanded upon from the basic cytotoxic tests to evaluate cell proliferation and migration potential. Two cell types were used for the cell proliferation and tracking study: mouse embryonic fibroblast cells (3T3) and human mesenchymal stem cells (hMSCs). Advanced microscopic methods allowed for the precise quantification of the function of both cell types. This study has demonstrated that a dose of nanoparticles lower than 20 µg·cm⁻² per area of the dish does not negatively affect the cells’ morphology, migration, cytoskeletal function, proliferation, potential for wound healing, and single-cell migration in comparison to standard CellTracker™ Green CMFDA (5-chloromethylfluorescein diacetate). A higher dose of nanoparticles could be a potential risk for cytoskeletal folding and detachment of the cells from the solid extracellular matrix. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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10 pages, 1990 KiB

Open AccessArticle

Ultrashort Echo Time Quantitative Susceptibility Mapping (UTE-QSM) of Highly Concentrated Magnetic Nanoparticles: A Comparison Study about Different Sampling Strategies

by Xing Lu, Hyungseok Jang, Yajun Ma, Saeed Jerban, Eric Y. Chang and Jiang Du

Molecules 2019, 24(6), 1143; https://doi.org/10.3390/molecules24061143 - 22 Mar 2019

Cited by 17 | Viewed by 3192

Abstract

The ability to accurately and non-invasively quantify highly concentrated magnetic nanoparticles (MNPs) is desirable for many emerging applications. Ultrashort echo time quantitative susceptibility mapping (UTE-QSM) has demonstrated the capability to detect high iron concentrations. In this study, we aimed to investigate the effect [...] Read more.

The ability to accurately and non-invasively quantify highly concentrated magnetic nanoparticles (MNPs) is desirable for many emerging applications. Ultrashort echo time quantitative susceptibility mapping (UTE-QSM) has demonstrated the capability to detect high iron concentrations. In this study, we aimed to investigate the effect of different sampling trajectories on the accuracy of quantification based on MNPs acquired through UTE-QSM. A phantom with six different MNP concentrations was prepared for UTE-QSM study with different UTE sampling trajectories, including radial acquisition, continuous single point imaging (CSPI), and Cones with four different gradient stretching factors of 1.0, 1.2, 1.4, and 1.6. No significant differences were found in QSM values derived from the different UTE sampling strategies, suggesting that the UTE-QSM technique could be accelerated with extended Cones sampling. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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16 pages, 5205 KiB

Open AccessArticle

A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia

by Idan Steinberg, Gil Tamir and Israel Gannot

Molecules 2018, 23(3), 670; https://doi.org/10.3390/molecules23030670 - 16 Mar 2018

Cited by 4 | Viewed by 2852

Abstract

Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. [...] Read more.

Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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3727 KiB

Open AccessArticle

In Vivo Dual-Modality Fluorescence and Magnetic Resonance Imaging-Guided Lymph Node Mapping with Good Biocompatibility Manganese Oxide Nanoparticles

by Yonghua Zhan, Wenhua Zhan, Hanrui Li, Xinyi Xu, Xu Cao, Shouping Zhu, Jimin Liang and Xueli Chen

Molecules 2017, 22(12), 2208; https://doi.org/10.3390/molecules22122208 - 12 Dec 2017

Cited by 19 | Viewed by 4804

Abstract

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T₁ contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy_7.5), which functions [...] Read more.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T₁ contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy_7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn₃O₄@PEG-Cy_7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn₃O₄@PEG-Cy_7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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2834 KiB

Open AccessFeature PaperArticle

Enhanced Methods to Estimate the Efficiency of Magnetic Nanoparticles in Imaging

by Ann M. Hirt, Monika Kumari, David Heinke and Alexander Kraupner

Molecules 2017, 22(12), 2204; https://doi.org/10.3390/molecules22122204 - 12 Dec 2017

Cited by 10 | Viewed by 4609

Abstract

Magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) are powerful methods in the early diagnosis of diseases. Both imaging techniques utilize magnetic nanoparticles that have high magnetic susceptibility, strong saturation magnetization, and no coercivity. FeraSpin^TM R and its fractionated products have [...] Read more.

Magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) are powerful methods in the early diagnosis of diseases. Both imaging techniques utilize magnetic nanoparticles that have high magnetic susceptibility, strong saturation magnetization, and no coercivity. FeraSpin^TM R and its fractionated products have been studied for their imaging performances; however, a detailed magnetic characterization in their immobilized state is still lacking. This is particularly important for applications in MPI that require fixation of magnetic nanoparticles with the target cells or tissues. We examine the magnetic properties of immobilized FeraSpin^TM R, its size fractions, and Resovist^®, and use the findings to demonstrate which magnetic properties best predict performance. All samples show some degree of oxidation to hematite, and magnetic interaction between the particles, which impact negatively on image performance of the materials. MRI and MPI performance show a linear dependency on the slope of the magnetization curve, i.e., initial susceptibility, and average blocking temperature. The best performance of particles in immobilized state for MPI is found for particle sizes close to the boundary between superparamagnetic (SP) and magnetically ordered, in which only Néel relaxation is important. Initial susceptibility and bifurcation temperature are the best indicators to predict MRI and MPI performance. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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935 KiB

Open AccessArticle

Magnetic Marking and Intraoperative Detection of Primary Draining Lymph Nodes in High-Risk Prostate Cancer Using Superparamagnetic Iron Oxide Nanoparticles: Additional Diagnostic Value

by Alexander Winter, Svenja Engels, Lena Reinhardt, Clara Wasylow, Holger Gerullis and Friedhelm Wawroschek

Molecules 2017, 22(12), 2192; https://doi.org/10.3390/molecules22122192 - 09 Dec 2017

Cited by 11 | Viewed by 6087

Abstract

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or [...] Read more.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/mL and/or Gleason score ≥ 8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes/lymph node metastases outside the established node template in high-risk PCa. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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Review

Jump to: Research

2899 KiB

Open AccessReview

Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues

by Federico D’Agata, Federico Alessandro Ruffinatti, Silvia Boschi, Ilaria Stura, Innocenzo Rainero, Ornella Abollino, Roberta Cavalli and Caterina Guiot

Molecules 2018, 23(1), 9; https://doi.org/10.3390/molecules23010009 - 21 Dec 2017

Cited by 59 | Viewed by 9703

Abstract

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic [...] Read more.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in—or are close to—clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity. Full article

(This article belongs to the Special Issue Applications of Magnetic Nanoparticles in Biomedicine)

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