A Stroke of Genius

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Science Translational Medicine  18 Jun 2014:
Vol. 6, Issue 241, pp. 241ec105
DOI: 10.1126/scitranslmed.3009594

The word “stroke” derives from its most dangerous characteristic: that it strikes suddenly, without warning. A stroke occurs when a part of the brain is cut off from its blood supply by a clot or broken blood vessel. Brain cells immediately begin to die at a rate of 2 million cells per minute, causing irreversible disability or death. Cerebral amyloid angiopathy (CAA) is a major contributor to stroke—especially in elderly people and in patients with Alzheimer’s disease. This condition is characterized by the deposition of amyloid-β proteins in the blood vessels of the brain and causes excessive inflammation, leading to hemorrhagic stroke. Although CAA can be treated with immunosuppressive steroids when detected early, it can only be diagnosed with a brain biopsy, leaving the problem frequently undiagnosed until catastrophic consequences arise. To overcome the challenge of detection and minimize systemic side effects of the immunosuppressive treatment, Agyare and colleagues engineered theranostic nanovehicles (TNVs) capable of targeting amyloid-β deposits to simultaneously enhance imaging modalities while locally delivering the drug.

The team prepared chitosan nanoparticles that incorporated a magnetic resonance imaging (MRI) contrast agent, a core of the immunosuppressant cyclophosphamide, and an outer shell of antibodies to amyloid-β. In in vitro experiments, TNVs effectively bound to amyloid-β proteins and reduced the secretion of inflammatory cytokines from endothelial cells typical of the inflamed blood brain barrier. In vivo, TNVs accumulated preferentially in brain arteries of mice pretreated with amyloid-β proteins, an important consequence of their amyloid-β–targeting surfaces, as compared with mice without these proteins. Most importantly, TNVs enhanced detection with MRI and computed tomography.

This new strategy may prove to be a useful tool for the clinical diagnosis and treatment of early CAA before it leads to hemorrhagic stroke. The TNVs will need to be evaluated for their ability to treat cerebral inflammation in a more stringent animal model of CAA, and the contrast enhancement could be improved for smaller blood vessels. However, the use of a single engineered nanoparticle for both treatment and imaging of CAA is an important step toward the prevention of one of the leading causes of death in the United States.

E. K. Agyare et al., Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits. J. Controlled Release 184, 121–129 (2014). [PubMed]

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