Oude Engberink, R.D., et al.: Comparison of SPIO and USPIO for in vitro labeling of human monocytes: MR detection and cell function. Radiology 243, 467-474
ABSTRACT To label human monocytes with superparamagnetic iron oxide (SPIO) and compare labeling efficiency with that of ultrasmall SPIO (USPIO) and evaluate the effect of iron incorporation on cell viability, migratory capacity, and proinflammatory cytokine production.
The study was approved by the institutional ethics committee; informed consent was obtained from donors. Freshly isolated human monocytes were labeled with iron particles of two sizes, USPIOs of 30 nm and SPIOs of 150 nm, for 1.5 hours in culture medium containing 0.1, 0.5, 1.0, and 3.7 mg of iron per milliliter. Labeling efficiency was determined with relaxation time magnetic resonance (MR) imaging (4.7 T) and Prussian blue staining for presence of intracellular iron. Cell viability was monitored; migratory capacity of monocytes after labeling was evaluated by using an in vitro assay with monolayers of brain endothelial cells. Levels of proinflammatory cytokines, interleukin (IL) 1 and IL-6, were measured with enzyme-linked immunosorbent assay 24 hours after labeling. Data were analyzed with Student t test or two-way analysis of variance followed by a multiple-comparison procedure.
R2 relaxation rates increased for cell samples incubated with SPIOs, whereas rates were not affected for samples incubated with highest concentration of USPIOs. Labeling monocytes with SPIOs (1.0 mg Fe/mL) resulted in an R2 of 13.1 sec(-1) +/- 0.8 (standard error of the mean) (7 sec(-1) +/- 0.2 for vehicle-treated cells, P < .05) and had no effect on cell viability. On the basis of T2 relaxation times, the in vitro MR detection limit of 58 labeled monocytes per 0.05 microL was calculated. Migration of labeled monocytes was not different from that of vehicle-treated cells. Intracellular iron had no effect on production of IL-1 and IL-6 24 hours after labeling.
In vitro labeling of human monocytes is effective by using SPIOs, not USPIOs. Incubation with SPIOs (1.0 mg Fe/mL) results in efficient labeling detectable on MR images and does not affect cellular viability and activation markers such as cell migration and cytokine production.
- SourceAvailable from: Achraf Al Faraj
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- "Iron oxide MNP with total size of 100 nm were preferred in this study as MNP in this range have been shown to be more effective for in vitro monocyte / macrophage labeling compared to smaller nanoparti - cles size ( Oude Engberink et al . 2007 ) . Zeta potential analysis has revealed that SPIO , SPIO – PEG , and SPIO – PEG – COOH have a surface charge of - 1 . 8 , - 3 . 3 , and - 5 . 8 mV , respectively . Ferrozine - based spectro - photometry ( Fig . 1 ) revealed higher uptake of iron by M2 macrophages compared to M1 subsets for the different SPIO nanoparticles ( i . e . , a"
ABSTRACT: Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of different diseases, which make them attractive vehicles to deliver contrast agents or drugs for diagnostic or therapeutic purposes. In this study, the effect of polyethylene glycol functionalization of magnetic iron oxide nanoparticles and their further surface modification with carboxylic groups on bone marrow-derived M1 and M2 macrophages phenotype, labeling efficiency, uptake mechanism, biocompatibility, and their in vivo MR detection was assessed. An enhanced labeling efficiency was observed for carboxylic surface-modified superparamagnetic iron oxide (SPIO) compared to PEGylated SPIO and to a higher extent to plain SPIO along with a higher uptake by M2 subsets. Magnetic nanoparticles were found located in the periphery of the vesicles dispersed in the cytoplasm in TEM. Investigation of the labeling mechanism by inhibiting different uptake pathways revealed that endocytosis via scavenger receptor A, a process known to be clathrin mediated, plays a central role in the cellular uptake kinetics of both macrophages subpopulations. Biocompatibility evaluation showed no variation in cell viability and mitochondrial membrane potential with a low release of ROS. Flow cytometry and measurement of iNOS and Arginase 1 activity as marker of M1 and M2 macrophages polarization confirmed that magnetic labeling of macrophages subsets did not affect their polarization. In addition, no variation was observed in the biodistribution of magnetic iron oxide-labeled M1 and M2 macrophages subsets when monitored using noninvasive magnetic resonance imaging with a better detection for the enhanced SPIO–PEG–COOH-labeled cells.Journal of Nanoparticle Research 07/2013; 15(7). DOI:10.1007/s11051-013-1797-9 · 2.28 Impact Factor
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- "This is due to their larger particle size ( > 50 nm) and negative surface charge, which lead to rapid elimination. Iron-loaded mononuclear cells can actively cross a relatively intact BBB in cases of an active inflammatory process (Oude Engberink et al, 2007), but because of their large size, SPIOs do not leak across BBB defects like free USPIOs (as in malignant gliomas). In the clinical setting, FDA-approved doses of ferumoxides (SPIOs) were given to 20 patients with intrinsic or metastatic brain tumors. "
ABSTRACT: Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood-brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 09/2009; 30(1):15-35. DOI:10.1038/jcbfm.2009.192 · 5.34 Impact Factor
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- "Although there are claims of detection at 10 ¡12 M (Gao and Hillebrenner 2008), present-day technologies involve a trade-oV between the SPIO imaging parameters including Weld strength, gradient characteristics, acquisition time (Kircher et al. 2003; Heyn et al. 2006) against the number of cells to be detected. Also there are diVerences in detection sensitivities between SPIOs and the ultrasmall SPIOs (USPIOs) (Engberink et al. 2007). Nano-and microparticles in the form of iron oxide particles are available commercially in streptavidin-conjugated form and can be used to target tumour cells (Artemov et al. 2003). "
ABSTRACT: Molecular imaging, first developed to localise antigens in light microscopy, now encompasses all imaging modalities including those used in clinical care: optical imaging, nuclear medical imaging, ultrasound imaging, CT, MRI, and photoacoustic imaging. Molecular imaging always requires accumulation of contrast agent in the target site, often achieved most efficiently by steering nanoparticles containing contrast agent into the target. This entails accessing target molecules hidden behind tissue barriers, necessitating the use of targeting groups. For imaging modalities with low sensitivity, nanoparticles bearing multiple contrast groups provide signal amplification. The same nanoparticles can in principle deliver both contrast medium and drug, allowing monitoring of biodistribution and therapeutic activity simultaneously (theranostics). Nanoparticles with multiple bioadhesive sites for target recognition and binding will be larger than 20 nm diameter. They share functionalities with many subcellular organelles (ribosomes, proteasomes, ion channels, and transport vesicles) and are of similar sizes. The materials used to synthesise nanoparticles include natural proteins and polymers, artificial polymers, dendrimers, fullerenes and other carbon-based structures, lipid-water micelles, viral capsids, metals, metal oxides, and ceramics. Signal generators incorporated into nanoparticles include iron oxide, gadolinium, fluorine, iodine, bismuth, radionuclides, quantum dots, and metal nanoclusters. Diagnostic imaging applications, now appearing, include sentinal node localisation and stem cell tracking.Histochemie 12/2008; 130(5):845-75. DOI:10.1007/s00418-008-0511-y · 2.93 Impact Factor