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Sci Transl Med ; 11(506)2019 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-31434756

RESUMEN

Nanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse to large rabbit and porcine atherosclerosis models, with an emphasis on the solutions we implemented to overcome production and evaluation challenges. Specifically, we integrated translational imaging readouts within our workflow to both analyze the nanoimmunotherapeutic's in vivo behavior and assess treatment response in larger animals. We observed our nanoimmunotherapeutic's anti-inflammatory efficacy in mice, as well as rabbits and pigs. Nanoimmunotherapy-mediated reduction of inflammation in the large animal models halted plaque progression, supporting the approach's translatability and potential to acutely treat atherosclerosis.


Asunto(s)
Aterosclerosis/inmunología , Aterosclerosis/terapia , Imagenología Tridimensional , Inmunoterapia , Nanomedicina , Animales , Apolipoproteínas E/deficiencia , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/toxicidad , Imagen por Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , Tomografía de Emisión de Positrones , Conejos , Simvastatina/farmacología , Simvastatina/uso terapéutico , Especificidad de la Especie , Porcinos , Distribución Tisular
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