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Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highly reliant on recanalization therapies, which are limited to only a subset of patients due to their narrow therapeutic window; hence, there is a huge need for new stroke treatments. Nonetheless, the vast majority of promising treatments are not effective in the clinical setting due to their inability to cross the blood-brain barrier and reach the brain. In this context, nanotechnology-based approaches such as nanoparticle drug delivery emerge as the most promising option. In this review, we will discuss the current status of nanotechnology in the setting of stroke, focusing on the diverse available nanoparticle approaches targeted to the different pathological and physiological repair mechanisms involved in each of the stroke phases.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor–related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-β. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

Biomedical applications of nanoparticles require a fundamental understanding of their interactions and behavior with biological interfaces. Protein corona formation can alter the morphology and properties of nanomaterials, and knowledge of the interfacial behavior of the complexes, using in situ analytical techniques, will impact the development of nanocarriers to maximize uptake and permeability at cellular interfaces. In this study we evaluate the interactions of acrylamide-based nanogels, with neutral, positive, and negative charges, with serum-abundant proteins albumin, fibrinogen, and immunoglobulin G. The formation of a protein corona complex between positively charged nanoparticles and albumin is characterized by dynamic light scattering, circular dichroism, and surface tensiometry; we use neutron reflectometry to resolve the complex structure at the air/water interface and demonstrate the effect of increased protein concentration on the interface. Surface tensiometry data suggest that the structure of the proteins can impact the interfacial properties of the complex formed. These results contribute to the understanding of the factors that influence the bio-nano interface, which will help to design nanomaterials with improved properties for applications in drug delivery.

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