Treating neurological disorders often demands overcoming the blood-brain barrier. Hijacking the active transport mechanisms of this tight, selective endothelial cell layer shows great promise in administering therapeutic agents to the brain. A potential carrier system needs to be well-defined, bio-compatible and able to display functional moieties for transcytosis. We designed and characterized temperature-responsive elastin-like peptide (ELP) nanoparticles that are highly monodisperse and stable. We have characterized ELP nanoparticles using multi-angle light scattering coupled to size-exclusion chromatography to determine their absolute molecular weight and aggregation number. The resulting micelles had hydrodynamic radii of 24.2 + 0.7 nm and consisted of 250 + 9 monomers with a total molecular weight of 12.0 + 0.4 MDa. We showed that the surface density of various ligands and targeting groups can be controlled by combining different ELPs prior to temperature-induced micelle formation. This affected cell binding, (endosomal) cell uptake and activity of attached groups. Both cell-penetrating peptides as well as nanobodies were reliably displayed on the micellar surface in combination with e.g. fluorophores and photosensitizers. We used the peptide G23, known to bind the ganglioside GM1b, resulting in transcytosis across the blood-brain barrier, as a targeting group to direct ELP nanoparticles to the brain. We show in vitro and in vivo results of G23-modified ELP nanoparticles and their ability to overcome the blood-brain barrier.

Elastin-like peptide nanoparticles for drug delivery to the brain

255th National Meeting (2018)

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