Editors' ChoiceCardiovascular Disease

Tasty solution to keeping arteries open

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Science Translational Medicine  31 Aug 2016:
Vol. 8, Issue 354, pp. 354ec141
DOI: 10.1126/scitranslmed.aah6077

Coronary artery disease (CAD) is the most common cause of death in the world, resulting in the loss of over 8 million lives in 2013 alone. During atherosclerotic CAD progression, localized inflammation causes plaque buildup, thickening of the arterial wall, and narrowing of the arterial lumen. Partial or complete blockage of the coronary arteries, which supply blood to the heart muscle, results in chest pain and/or myocardial infarction (heart attack) due to acute ischemia. The most common methods to treat CAD use minimally invasive percutaneous techniques, such as balloon dilation, tissue excision, and/or stenting to widen the artery and improve blood flow. Although percutaneous techniques are initially successful at reestablishing proper blood flow, the underlying atherosclerosis remains untreated and causes vessel re-obstruction or restenosis in 30 to 40% of patients. Systemic therapeutic regimens to directly treat atherosclerosis have shown limited efficacy as a result of poor drug accumulation at the disease site and rapid drug excretion. In a recent study, Feng et al. provide evidence that specific modifications can be used to create inflammation-sensitive nanoparticles that can target arterial damage, delivering immunomodulatory drugs locally to suppress vessel restenosis.

Previous attempts to engineer atherosclerosis-targeting delivery devices have shown tremendous promise but often require the use of expensive components, such as peptides and aptamers, which greatly reduce their cost-benefit potential. Feng et al. developed an inexpensive alternative strategy that chemically modifies drug-loaded composite carbohydrate/fat nanoparticles to confer stimuli sensitivity. Through the use of either acetalation or boronic ester attachment, the rapamycin-loaded nanoparticles disassemble and release their payloads in the presence of acidic pH or hydrogen peroxide (H2O2), two stimuli associated with the inflammatory microenvironment of atherosclerotic plaques. The authors showed that their modified nanoparticles were endocytosed and intracellularly processed by rat aortic vascular smooth muscle cells more efficiently than control, stimuli-insensitive polyester nanoparticles. When treated with intravenously delivered rapamycin-loaded stimuli-sensitive nanoparticles, rats that had been subjected to carotid artery balloon injury showed minimal arterial restenosis. In contrast, animals receiving soluble drug or drug delivered by the control, stimuli-insensitive polyester nanoparticles showed a more limited capacity to prevent vessel narrowing.

Additional studies will be needed to investigate the synergy of pH- and H2O2-sensitivity and the in vivo mechanisms of nanoparticle targeting. Nevertheless, the research by Feng et al. provides considerable evidence for the utility of their inexpensive engineered system to target injured vasculature and its future potential for the prevention of CAD relapse.

S. Feng et al., Nanoparticles responsive to the inflammatory microenvironment for targeted treatment of arterial restenosis. Biomaterials 105, 167–184 (2016). [Abstract]

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