<i>In Vivo</i>MRI of Functionalized Iron Oxide Nanoparticles for Brain Inflammation

Tang, Tang; Valenzuela, Anthony; Petit, Fanny; Chow, Sarah; Leung, Kevin H.; Gorin, Fredric A; Louie, Angelique Y.; Dhénain, Marc

doi:10.1155/2018/3476476

Cited by 30 publications

(20 citation statements)

References 53 publications

(50 reference statements)

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“…Due to their cysteine-rich binding sites, SR-As recognize polyanionic ligands through electrostatic interactions. This includes dimercaptosuccinic acid (DMSA) [ 152 ], carboxy-dextran [ 147 ], and dextran sulfate [ 149 ]. Novel PEG-coated IONs conjugated with thymidine-rich DNA oligonucleotides were recently developed for macrophage labeling and atherosclerotic plaque detection in vivo by exploiting their enhanced recognition by SR-As [ 146 ].…”

Section: Enhancing Ion Internalizationmentioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.

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Section: Enhancing Ion Internalizationmentioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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“…In our study, we found satisfactory viability values using a 4-h labeling time (99.3%, 99.6% and 98.6% for the respective M-SPION concentrations of 10, 30 and 50 µg Fe/mL). In studies on granulocyte and leukocyte-labeling with SPIONs, the incubation time was reported to be between 1 and 4 h for labeling [51,54,57,59,61,62,85,86]. For example, in the study of Tang et al [61], an incubation time of 3 h was best for the clinical application of these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies employing exogenously labeled granulocytes to analyze infection or inflammation processes have used SPIONs with different strategies [51,54,[57][58][59][60][61][62]. SPIONs, when coupled with near-infrared spectrum fluorophores, enhance pathological assessments due to the sensitivity or specificity of the complementary information provided by the optical imaging modality [63], enabling multimodal imaging [64,65].…”

Section: Introductionmentioning

confidence: 99%

Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles

et al. 2020

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This in vitro study aimed to find the best method of granulocyte isolation for subsequent labeling with multimodal nanoparticles (magnetic and fluorescent properties) to enable detection by optical and magnetic resonance imaging (MRI) techniques. The granulocytes were obtained from venous blood samples from 12 healthy volunteers. To achieve high purity and yield, four different methods of granulocyte isolation were evaluated. The isolated granulocytes were labeled with multimodal superparamagnetic iron oxide nanoparticles (M-SPIONs) coated with dextran, and the iron load was evaluated qualitatively and quantitatively by MRI, near-infrared fluorescence (NIRF) and inductively coupled plasma mass spectrometry (ICP-MS). The best method of granulocyte isolation was Percoll with Ficoll, which showed 95.92% purity and 94% viability. After labeling with M-SPIONs, the granulocytes showed 98.0% purity with a yield of 3.5 × 10 6 cells/mL and more than 98.6% viability. The iron-loading value in the labeled granulocytes, as obtained by MRI, was 6.40 ± 0.18 pg/cell. Similar values were found with the ICP-MS and NIRF imaging techniques. Therefore, our study shows that it is possible to isolate granulocytes with high purity and yield and labeling with M-SPIONs provides a high internalized iron load and low toxicity to cells. Therefore, these M-SPION-labeled granulocytes could be a promising candidate for future use in inflammation/infection detection by optical and MRI techniques.Hard-to-reach or occult inflammation and infection processes are clinically challenging. Their clinical diagnoses involve biochemical and radiological examinations, but these methods can produce false negatives [11][12][13][14][15]. To determine the localization, extent and severity of inflammation, imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) can be performed but have limitations in the early stages of the disease, as they are dependent on morphological changes [16][17][18]. Accurate and early diagnosis of inflammation and infection helps reduce mortality and morbidity and increase drug treatment success [19][20][21].Proinflammatory effects help leukocytes migrate from the blood vessel to the site of injury, due to increased vascular permeability through stimulation by cytokines and interleukins. There is an initial accumulation of granulocytes, mainly neutrophils, in the inflamed area and later of lymphocytes and macrophages [22][23][24]. Granulocytes are the most abundant subset of leukocytes [25] and are produced in the bone marrow, originating from myeloid precursor cells and undergoing a maturing process before they are able to perform their functions, mainly phagocytosis [25,26]. They differ from other cells in that they have granules with proteolytic enzymes that fight microorganisms or other inflammatory agents [25,27]. Granulocytes are considered frontline cells in inflammation and infection processes [28]. In many cases, to detect inflammation/infection, it is necessary to label isolated granulocyte...

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“…With its ability to image during the lifetime of the subject, whether animal or human, MRI can be used in experimental settings to investigate disease progression longitudinally, which can then be correlated with postmortem immunostaining for microglia and monocytes (Neuwelt et al, 2009), in addition to various disease hallmarks (Justicia et al, 2008;Jacobs et al, 2012;Tang et al, 2018;Yi et al, 2019). In a rat model of glioma, tumors were imaged during growth progression while studying the microglial/macrophagic changes visualized using ultrasmall superparamagnetic iron oxides (USPIOs).…”

Section: Mrimentioning

confidence: 99%