In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
Agulla, Jesús (Universidade de Santiago de Compostela)
Brea, David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Campos, Francisco (Universidade de Santiago de Compostela)
Sobrino, Tomás (Universidade de Santiago de Compostela)
Argibay, Bárbara (Universidade de Santiago de Compostela)
Al-Soufi, Wajih (Universidade de Santiago de Compostela)
Blanco, Miguel (Universidade de Santiago de Compostela)
Castillo, José (Universidade de Santiago de Compostela)
Ramos-Cabrer, Pedro (Universidade de Santiago de Compostela)

Data:	2013
Resum:	The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases.
Ajuts:	Instituto de Salud Carlos III PI11-02161 Instituto de Salud Carlos III CP09-00074 Ministerio de Economía y Competitividad SAF2008-02190 Ministerio de Economía y Competitividad SAF2011-30517 Ministerio de Economía y Competitividad RETICS-INVICTUS/R012-0014
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cerebral ischemia ; Peri-infarct region ; MRI ; Theranostics ; Drug delivery
Publicat a:	Theranostics, Vol. 4 (december 2013) , p. 90-105, ISSN 1838-7640

DOI: 10.7150/thno.7088
PMID: 24396517

16 p, 2.9 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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