Theranostics 2014; 4(1):90-105. doi:10.7150/thno.7088
In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
1. Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, E-15706 Santiago de Compostela, Spain.
2. Research Unit, University Hospital of Salamanca and Institute of Health Sciences of Castilla and Leon, E-37007 Salamanca, Spain.
3. Cellular and Molecular Neurobiology Research Group and Grup de Recerça en Neurociencies del IGTP, Department of Neurosciences, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias I Pujol-Universitat Autónoma de Barcelona, E-08916 Badalona, Spain.
4. Single Molecule Fluorescence Research Unit, Department of Physical Chemistry, Faculty of Science, University of Santiago de Compostela, E-27002 Lugo, Spain.
* These two authors have contributed equally to this work.
Agulla J, Brea D, Campos F, Sobrino T, Argibay B, Al-Soufi W, Blanco M, Castillo J, Ramos-Cabrer P. In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia. Theranostics 2014; 4(1):90-105. doi:10.7150/thno.7088. Available from http://www.thno.org/v04p0090.htm
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.
Keywords: cerebral ischemia, peri-infarct region, MRI, Theranostics, Drug delivery.