Nanoparticle transport through the blood brain barrier in health and disease

People involved: Alberto Redaelli, Marco Rasponi, Stefano Ugolini, Paola Occhetta, Roberta Visone.

Funding source: CARIPLO Foundation

Grant number: 2013-1048

Funding period: 2013 - 2015

Partners: Politecnico di Milano, Fondazione IRCCS Istituto Neurologico Carlo Besta (BESTA), Istituto FIRC di Oncologia Molecolare (IFOM)

The blood brain barrier (BBB) separates the central nervous system (CNS) parenchyma from the vascular compartment and plays a crucial role in regulating the trafficking of nanoparticles and drugs which may occur either actively (receptor mediated) or passively (membrane disruption). As a matter of fact, BBB is also considered the main obstacle in efficient treatment of brain diseases such as cerebral tumors, Alzheimer, Parkinson disease, multiple sclerosis or stroke.

The nanoBBB project is aimed at increasing the knowledge about i) the interaction of nanoparticles (NPs) with the BBB and their mechanisms of penetration, ii) the identification of parameters and blood-borne proteins which can facilitate the up-take of these particles, and iii) the possible toxicity of the nanoparticles to endothelial cells; especially to the brain, a possible break-down of the barrier function and/or ultimately apoptosis of single cells from the network can lead to severe inflammatory diseases or even neurodegeneration.

For this purpose, an in vitro BBB endothelium model is being developed based on microscale technologies, which allows investigating the passage through the BBB of different brain areas and origins (brain stem, right/left hemisphere, cortex, male/female, old/young) from healthy and diseased (more specifically stroke) brains.