42 research outputs found
Modulation of the macrophage function in the hematopoietic niche by using engineered RBCs
Intravascular contrast agents in diagnostic applications: Use of red blood cells to improve the lifespan and efficacy of blood pool contrast agents
In medicine, discrimination between pathologies and normal areas is of great
importance, and in most cases, such discrimination is made possible by novel
imaging technologies. Numerous modalities have been developed to visualize tissue
vascularization in cardiovascular diseases or during angiogenic and vasculogenic
processes. Here, we report the recent advances in vasculature imaging, providing
an overview of the current non-invasive approaches in biomedical diagnostics
and potential future strategies for prognostic assessment of vessel diseases, such
as aneurysms and coronary artery occlusion leading to myocardial infarction.
There are several contrast agents (CAs) available to improve the visibility of specific
tissues at the early stage of diseases, allowing for rapid treatment. However,
CAs are also hampered by numerous limitations, including rapid diffusion from
blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation
from blood vessels leads to a rapid loss of the image. If the contrast medium can
fully be confined to the vascular space, high-resolution structural and functional
vascular imaging could be obtained. Many scientists have contributed new
materials and/or new carrier systems. For example, the use of red blood cells
(RBCs) as CA-delivery systems appears to provide a scalable alternative to current
procedures that allows adequate vascular imaging. Recognition and removal of
CAs from the circulation can be prevented and/or delayed by using RBCs as
biomimetic CA-carriers, and this technology should be clinically validated
Dexamethasone restrains ongoing expression of interleukin-23p19 in peripheral blood-derived human macrophages.
BACKGROUND:
Since its recent discovery, interleukin-23 has been shown to be involved in the pathogenesis of autoimmune diseases favoring the development of a T cell subset referred to as T helper 17. Glucocorticoids are widely employed in inflammatory and autoimmune diseases as they inhibit pro-inflammatory signaling and prevent production of inflammation mediators. Very limited information is available about the efficacy of synthetic glucocorticoids in containing the expression of interleukin-23 under cell activation.
RESULTS:
We demonstrate here that the glucocorticoid analogue dexamethasone administered to human monocyte-derived macrophages is indeed able to restrain the expression of interleukin-23 once it has been triggered by a pro-inflammatory stimulus. This effect of dexamethasone is here demonstrated being secondary to suppression of p38 MAPK activity, and involving a protein phosphatase--likely MAPK phosphatase-1 (MKP-1).
CONCLUSIONS:
Results reported in this paper show that a 10 nanomolar dose of dexamethasone not only prevents inflammatory activation but is also efficacious in confining active inflammation. This effect is here demonstrated not to occur through "canonical" inhibition of the NF-ÎşB transcription factor but through a distinct cascade of down-modulation, that underlines the importance of the transactivating activity of glucocorticoid receptor in the context of its anti-inflammatory action
Magnetic red blood cells as new contrast agents for MRI applications
Superparamagnetic iron oxide (SPIO) nanoparticles have been produced and used successfully as potent contrast agents for Magnetic Resonance Imaging (MRI). However, a significant challenge associated with the biological application of SPIO-tracer agents is their behavior in vivo since their efficacy is often compromised due to a rapid recognition and clearance by the reticuloendothelial system (RES) which limits the applicability of such compounds in MRI. The advances in nanotechnology and molecular cell biology had lead to improve stability and biocompatibility of these nanoparticles, but despite a number of efforts, the SPIO half-life in blood circulation is very short. In this contest, the potential of red blood cells (RBCs) loaded with SPIO nanoparticles as a tracer material for MRI has been investigated in order to realize a blood pool tracer with longer blood retention time. Previously, we have proposed the encapsulation into RBCs of superparamagnetic iron oxide nanoparticles carboxydextran coated, such as Resovist contrast agent. This approach led to a nanoparticle reduction in uptake by the RES, increasing the blood circulation half-life of nanoparticles. Recently, the loading procedure was applied to a new contrast agent, the P904 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles coated by hydrophilic derivatives of glucose, recently developed by Guerbet Laboratories. The results evidenced that this nanomaterial can be efficiently loaded into human and murine RBCs at concentrations ranging from 1.5 to 12 mM Fe. In vivo experiments performed in mice have showed an increased survival in the mouse vascular system of P904 encapsulated into RBCs respect to free P904 sample intravenously injected at the equivalent amounts
Encapsulation of new ferucarbotran nanoparticles into red blood cells as potential MPI contrast agent
New biomimetic constructs for improved in vivo circulation of superparamagnetic nanoparticles
none5noSuperparamagnetic iron oxide nanoparticles (SPIOs) have been produced and used as a potent and versatile contrast media for magnetic resonance imaging (MRI). Despite a number of efforts to improve their surface chemistry and biocompatibility, the SPIOs half life in blood circulation is very short and they are rapidly taken up by the reticuloendothelial system (RES). In this paper we describe a new method that permits to avoid the rapid clearance of SPIOs. Nanoparticles are made biocompatible by encapsulation into autologous red blood cells. These biomimetic constructs preserve the main properties of the cells that escape RES clearance as well as the properties of the nanoparticles that perform even better than in blood suspension with reduced T 2*. These SPIO-loaded RBCs are promising intravascular imaging contrast agents and could also be addressed to selected body compartments by an external magnetic field.noneAntonelli, A.; Sfara, C.; Mosca, L.; Manuali, E.; Magnani, M.Antonelli, A.; Sfara, C.; Mosca, L.; Manuali, E.; Magnani, M
Ferucarbotran-loaded red blood cells as long circulating MRI contrast agents: first in vivo results in mice
The encapsulation of superparamagnetic iron oxide contrast agents in red blood cells (RBCs) could overcome their rapid removal by reticulo-endothelial system improving their stability in blood circulation
Encapsulation of superparamagnetic nanoparticles into red blood cells as new carriers of MRI contrast agents
Aims: The half-life of superparamagnetic iron oxide nanoparticles in the bloodstream is very short since they are rapidly taken up by the reticuloendothelial system. In this article, we report the encapsulation of different magnetic nanoparticles into human erythrocytes to increase their blood circulation time. Materials & methods: Newly synthesized and commercially available nanoparticles were evaluated for the encapsulation into red blood cells through the transient opening of membrane pores by controlled hypotonic dialysis and successive isotonic resealing and reannealing of cells. Results: Commercial superparamagnetic iron oxide nanoparticles (SHU 555A, AMI 227 and PMP-50) dextran or carboxydextran coated can be successfully loaded into red blood cells; similarly, some of the new nanomaterials, such as Np-1 nanoparticles dispersed in the DisperbykÂŽ-190 agent, can be efficiently encapsulated into red blood cells. Conclusion: A careful consideration of magnetic nanoparticles parameters, such as size, synthesis protocols, coating and/or dispersant agents, is required in order to obtain efficient loading through the cell membrane pores