Nowadays Alzheimer’s disease (AD) is the main cause of dementia in developed countries. The rise in life expectancy and the progressive ageing of the population are leading to an increased social and economic burden due to this illness. Unfortunately, this data is expected to increase in the upcoming years. Abnormal accumulation of intracellular tau protein and the extracellular aberrant deposits of beta-amyloid protein are the classic hallmarks of this disease. Traditionally the diagnosis and therapy efforts in this field were focused to one of these paths. All of these attempts failed to provide a suitable treatment because most of them, despite being a good strategy, were raised in an inappropriate time. Here we propose a theragnostic approach to overcome these limitations. Our goal is to achieve a multimodal and versatile nanoplatform compatible with several functionalizations which can be vectorised to an AD early stage biomarker, and used in non-invasive technologies as MRI and PET. Our aim is to take advantage of the iron oxide nanoparticles, which has been largely proved in biomedical applications due to their suitability as contrast agent and biocompatibility. For that purpose our nanoparticles are doped with zinc and manganese1, stabilized with oleic acid/oleylamine in organic solvents, and transferred to the aqueous phase by an amphiphilic polymer coating (dodecyl-grafted-poly(isobutylene-alt-maleicanhydride, in the following referred to as PMA)2. Modified-PMA confers colloidal stability to the NPs in high ionic strength media and provides several chemical groups (e.g., carboxyl, dibenzocyclooctyne, furfuryl, etc.) for further functionalization with other macromolecules, including homing antibodies, polyethylene glycol, and imaging agents as PET radiotracers and fluorescence markers.

Multimodal nanostructures as theragnostic agent in Alzheimer disease at early stages: PANA project

2019 Fall National Meeting

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