RESUMEN
Information about the in vivo location, shape, degradation, or erosion rate of injected in situ gelating hydrogels can be obtained with magnetic resonance imaging (MRI). Herein, an injectable supramolecular ureidopyrimidinone-based hydrogel (UPy-PEG) is functionalized with a modified Gadolinium(III)-DOTA complex (UPy-Gd) for contrast enhanced MRI. The contrast agent is designed to supramolecularly interact with the hydrogel network to enable high-quality imaging of this hydrogel. The applicability of the approach is demonstrated with successful visualization of the Gd-labeled UPy-PEG hydrogel after targeted intramyocardial catheter injection in a pig heart.
Asunto(s)
Materiales Biocompatibles , Medios de Contraste , Corazón/diagnóstico por imagen , Hidrogeles , Imagen por Resonancia Magnética , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Materiales Biocompatibles/farmacología , Medios de Contraste/química , Medios de Contraste/farmacocinética , Medios de Contraste/farmacología , Femenino , Gadolinio/química , Gadolinio/farmacocinética , Gadolinio/farmacología , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Pirimidinonas/química , Pirimidinonas/farmacocinética , Pirimidinonas/farmacología , PorcinosRESUMEN
The field of molecular imaging aims to visualize and quantify (patho)physiological processes at the cellular and molecular level. Sensitive and site-targeted contrast agents are employed to visualize molecular constituents of processes of interest. The principal aim of this study was to develop a magnetic resonance imaging (MRI) detectable liposome with high relaxivity and stability. To this end, Gd(III)DOTA-DSPE was synthesized and incorporated in a liposomal formulation. The resulting liposomes were extensively characterized in vitro in terms of contrast agent efficiency and structural properties. The liposomes were shown to have a high longitudinal relaxivity, which is crucial for the detection of low concentration molecular markers in molecular imaging studies. We also demonstrated that Gd(III)DOTA-DSPE exhibits no detectable transmetallation upon incubation with Zn(II). This is important as it significantly contributes to the biocompatibility of the contrast agent. The present liposome preparation will serve as versatile and well characterized platform for molecular imaging and targeted drug delivery studies.
Asunto(s)
Medios de Contraste , Liposomas , Imagen por Resonancia Magnética , Compuestos Organometálicos , Fosfatidiletanolaminas , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Biology often uses hierarchical self-assembly to produce complex functional structures from smaller components. At each level of this stepwise process, non-covalent interactions bring together the subunits of a lower level of complexity, using the information encoded in their structures. Applying this approach to synthetic systems represents a formidable challenge, because it requires a high degree of command of non-covalent interactions. In this tutorial review, recent developments in the hierarchical self-assembly of discrete columnar aggregates are discussed.