Nanotoday 2019 - Abstract

Biomimetic nanoscavengers with enhanced neuroprotective properties against post-ischemic stroke effects

Christos Tapeinos¹, Matteo Battaglini^1,2, Attilio Marino¹, Ivana Cavaliere³, Gianni Ciofani^1,3

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

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INTRODUCTION

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.

METHODS

The biomimetic nanoscavengers (BIONICS) were composed of porcine-extracted brain lipids and their fabrication was achieved using a hot-emulsion ultra-sonication method. Their colloidal stability was studied in various biologically-relevant media, while their antioxidant ability was studied using EPR and various antioxidant assay kits. The ability of the nanoscavengers to cross the blood-brain barrier and be internalized by neurons was tested using a triple 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, while EPR results showed that the nanoscavengers demonstrated 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.

CONCLUSION

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.

ACKNOWLEDGMENTS
"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".