A new bio-inspired delivery platform to overcome blood brain barrier

Abstract

Event Abstract Back to Event A new bio-inspired delivery platform to overcome blood brain barrier Daniela Guarnieri1, 2, Ornella Muscetti1, 2 and Paolo Netti1, 2 1 Istituto Italiano di Tecnologia, Center for Advanced Biomaterials for Health Care, Italy 2 University of Naples Federico II, Centro di Ricerca Interdipartimentale sui Biomateriali - CRIB, Italy Endocytosis is the main internalization mechanism of cells[1]. Once endocytosed, the extracellular cargoes become entrapped in endosomes and are usually degraded into the lysosomes[1]-[3]. Therefore, a key step to achieve an effective drug-based therapy is to facilitate endosomal escape and ensure delivery of therapeutics across biological barriers. The relatively recent discovery that synthetic peptides can be used to transport biologically active molecules inside live cells has paved the way for developing new effective strategies for drug delivery into the brain[4]. In this work, starting from a bio-inspired approach, we designed a new delivery platform based on the use of a membranotropic peptide gH625, derived from the envelope of the Herpes simplex virus 1, to overcome the blood brain barrier (BBB). In particular, we conjugated gH625 to the surface of 50 and 100 nm amine-modified fluorescent polystyrene nanoparticles. Uptake mechanism, nanotoxicity and permeation across in vitro BBB models of gH625-functionalized NPs were studied. At early incubation times, the uptake of NPs with gH625 by brain endothelial cells is greater than that of the NPs with a control peptide, thanks to the high affinity of gH625 with cell membrane lipids, and their intracellular motion is mainly characterized by a random walk behavior. Most importantly, gH625 peptide promotes endo-lysosomal escape thus reducing intracellular accumulation as large aggregates of NPs. As a consequence of this mechanism, gH625 significantly decreases NP cytotoxic effect in several cell types[5] and enhances NP crossing of BBB[6] (Fig. 1). The results presented in our studies [5],[6] suggest that the gH625 platform may play a relevant role in overcoming biological barriers and could be used as a safe and effective delivery system for the transport of drugs across the BBB by providing high efficacy and extreme flexibility with unlimited targets.