• Drechsler, Markus
• Angelova, Angelina
• Angelov, Borislav
• Garamus, Vasil M.

Abstract

Structural control over design and formation of selfassembled nanomaterials for neuroprotection and neuroregeneration is crucial for their application in nanomedicine. Here a synthetic construct of the pituitary adenylate cyclase-activating polypeptide (PACAP38) coupled to a docosahexaenoic acid (DHA: an ω-3 polyunsaturated fatty acid (PUFA)) is designed towards the creation of compartmentalized liquid crystalline assemblies of neuroprotective compounds. The hormone PACAP38 is a ligand of the class B PAC1 G-protein-coupled receptor (GPCR), whereas DHA is a lipid trophic factor. The lipidated peptide PACAP-DHA is co-assembled into hierarchical nanostructures elaborated from hybrid vesicle-micelle reservoirs as well into PEGylated cubosomes composed of multiple neuroprotective building blocks. The resulting nanostructures are determined by synchrotron small-angle X-ray scattering (BioSAXS) and cryogenic transmission electron microscopy (cryo-TEM). Multicompartment topologies are obtained in a twofold approach: (i) intriguing compartmentalized vesicles, which embed pep-lipid micelles forming nanopatterns, and (ii) multidomain pep-lipid cubosomes. Both kinds of topologies are favorable for sustainedrelease applications in combination therapies of neurodegeneration. The organizational complexity of the scaffolds involving the lipidated high-molecular weight peptide hormone is beyond the one that has been reached with small lipid-like peptide surfactants.

Topics

• impedance spectroscopy
• compound
• transmission electron microscopy
• forming
• molecular weight
• self-assembly
• surfactant
• X-ray scattering