Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that...Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.展开更多
In the late 1980s,superparamagnetic iron oxide nanoparticles（SPIO）moved into focus as contrast agents in magnetic resonance imaging（MRI）,due to their strong relaxivity and resulting higher resolution of images.At ...In the late 1980s,superparamagnetic iron oxide nanoparticles（SPIO）moved into focus as contrast agents in magnetic resonance imaging（MRI）,due to their strong relaxivity and resulting higher resolution of images.At the time,no one anticipated their high potential in basic research or for medical diagnostic andtreatment. Since then, SPIO have been evaluated notonly as spe- cific markers for MRI, but also for cell labeling and tracking （Li et al., 2013）.展开更多
Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix prote...Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix proteins（O’Donnell et al.,2009）.Furthermore,the discovery of a broad spectrum of growth-promoting cues has led to novel concepts for thera-peutic strategies.展开更多
Background Magnetic resonance （MR） molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor （EGFR） plays an important role in the d...Background Magnetic resonance （MR） molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor （EGFR） plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. Methods We attached ultra-small superparamagnetic iron oxide （USPIO） particles to cetuximab （C225） anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry （SP） was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 pg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy （TEM）. We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging （MRI） scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. Conclusions We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.展开更多
基金supported by Deutsche Forschungsgemeinschaft(DFG)grant Klinische Forschergruppe(KFO)213(to JG).
文摘Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.
基金supported by deutsche Forschungsgemeinschaft Grant Klinische Forschungsgruppe 213 to JG
文摘In the late 1980s,superparamagnetic iron oxide nanoparticles（SPIO）moved into focus as contrast agents in magnetic resonance imaging（MRI）,due to their strong relaxivity and resulting higher resolution of images.At the time,no one anticipated their high potential in basic research or for medical diagnostic andtreatment. Since then, SPIO have been evaluated notonly as spe- cific markers for MRI, but also for cell labeling and tracking （Li et al., 2013）.
文摘Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix proteins（O’Donnell et al.,2009）.Furthermore,the discovery of a broad spectrum of growth-promoting cues has led to novel concepts for thera-peutic strategies.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30470525）.
文摘Background Magnetic resonance （MR） molecular imaging can detect abnormalities associated with disease at the level of cell and molecule. The epidermal growth factor receptor （EGFR） plays an important role in the development of lung cancer. This study aimed to explore new MR molecular imaging targeting of the EGFR on lung cancer cells. Methods We attached ultra-small superparamagnetic iron oxide （USPIO） particles to cetuximab （C225） anti-human IgG using the carbodiimide method. We made the molecular MR contrast agents C225-USPIO and IgG-USPIO, the latter as a control reagent, and determined concentrations according to the Fe content. Lung cancer A549 cells were cultured and immunocytochemistry （SP） was used to detect the expression of EGFR on cells. We detected the binding rate of C225-USPIO to A549 cells with immunofluorescence staining and flow cytometry. We cultured A549 cells with C225-USPIO at a Fe concentration of 50 pg/ml and assayed the binding of C225-USPIO after 1 hour with Prussian blue staining and transmission electron microscopy （TEM）. We determined the effects on imaging of the contrast agent targeted to cells using a 4.7T MRI. We did scanning on the cells labeled with C225-USPIO, IgG-USPIO, and distilled water, respectively. The scanning sequences included axial T1WI, T2WI. Results Immunocytochemical detection of lung cancer A549 cells found them positive for EGFR expression. Immunofluorescence staining and flow cytometry after cultivation with different concentrations of C225-USPIO showed the binding rate higher than the control. Prussian blue staining and transmission electron microscopy revealed that in the C225-USPIO contrast agent group of cells the particle content of Fe in cytoplasmic vesicles or on surface was more than that in the control group. The 4.7T MR imaging （MRI） scan revealed the T2WI signal in the C225-USPIO group of cells decreased significantly more than in unlabeled cells, but there was no significant difference between the time gradients. Conclusions We successfully constructed the molecular imaging agent C225-USPIO targeting the EGFR of A549 lung cancer cells. The imaging agent showed good targeting effect and specificity, and reduced MRI T2 value significantly, thus such molecular contrast agents could provide a new way to measure EGFR levels.
