Brain-derived lipidic nanoparticles with enhanced neuroprotective properties for the treatment of cerebral ischemia
Christos Tapeinos1, Matteo Battaglini1,2, Attilio Marino1, Gianni Ciofani1,3
1 Smart Bio-Interfaces, Istituto Italiano di Tecnologia, Pontedera (PI), Italy
2The Biorobotics Institute, Scuola Superiore Sant’Anna, Pontedera (PI), Italy
3 Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy
Ischemic stroke occurs due to the reduced perfusion to a brain region, resulting in death or permanent neurological deficits. Unfortunately, to date, no effective treatment has been found to prevent damage to the ischemic brain after stroke. In view of this, we hypothesized that the targeted delivery of antioxidant (CeO2) nanoparticles (NPs) and iNOS inhibitors (i.e. L-NIL) will reduce the overproduced ROS and RNS in the ischemic area, resulting to the amelioration of the neurological deficits caused by oxidative stress.
The biomimetic nanoscavengers (BIONICS) were composed of porcine-extracted brain lipids and their fabrication was achieved using a hot-emulsion solvent-exchange method. Their colloidal stability was studied in various biologically-relevant media, while their antioxidant ability was studied various antioxidant assay kits. The ability of the nanoscavengers to cross the blood-brain barrier and be internalized by neurons was tested using an in vitro cell culture model consisting of human astrocytes, endothelial cells, and neurons, while their ability to inhibit oxidative stress in vitro was evaluated under hypoxic and normoxic conditions.
RESULTS AND DISCUSSION
BIONICS (~150 nm) presented excellent colloidal stability in water and biologically-relevant media, as well as excellent antioxidant capacity, similar to the one of the plain CeO2 NPs. Flow cytometry results demonstrated a time-dependent internalization of BIONICS as well as a neuroprotective and pro-neurogenic effect towards differentiated neuronal cells.
BIONICS demonstrated excellent colloidal stability and antioxidant capacity, resulting in the inhibition of ROS and RNS mediated oxidative stress, and in subsequent neuroprotection of astrocytes, endothelial and neuronal cells under conditions mimicking the post-ischemic stroke environment.
"This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 793644".