Multifunctional Superparamagnetic Stiff Nanoreservoirs for Blood Brain Barrier Applications

摘要

Neurological diseases (Alzheimer’s disease, Parkinson’s disease, and stroke) are becoming a major concern for health systems in developed countries due to the increment of ageing in the population, and many resources are devoted to the development of new therapies and contrast agents for selective imaging. However, the strong isolation of the brain by the brain blood barrier (BBB) prevents not only the crossing of pathogens, but also a large set of beneficial drugs. Therefore, an alternative strategy is arising based on the anchoring to vascular endothelial cells of nanoplatforms working as delivery reservoirs. In this work, novel injectable mesoporous nanorods, wrapped by a fluorescent magnetic nanoparticles envelope, are proposed as biocompatible reservoirs with an extremely high loading capacity, surface versatility, and optimal morphology for enhanced grafting to vessels during their diffusive flow. Wet chemistry techniques allow for the development of mesoporous silica nanostructures with tailored properties, such as a fluorescent response suitable for optical studies, superparamagnetic behavior for magnetic resonance imaging MRI contrast, and large range ordered porosity for controlled delivery. In this work, fluorescent magnetic mesoporous nanorods were physicochemical characterized and tested in preliminary biological in vitro and in vivo experiments, showing a transversal relaxivitiy of 324.68 mM⁻¹ s⁻¹, intense fluorescence, large specific surface area (300 m² g⁻¹), and biocompatibility for endothelial cells’ uptake up to 100 µg (in a 80% confluent 1.9 cm² culture well), with no liver and kidney disability. These magnetic fluorescent nanostructures allow for multimodal MRI/optical imaging, the allocation of therapeutic moieties, and targeting of tissues with specific damage.