Nanoassemblies formed by ultrashort peptides for the vehiculation of hydrophobic molecules

Over the last several decades, many papers report on spontaneous supramolecular assembly into ordered nanostructures with a variety of morphologies and this number is still expanding1. Among self-assembled supramolecules, peptides have attracted a great attention for biological applications due to their versatility and interesting chemical properties. In particular, our group is focused on the study of self-assembly of ultrashort peptides containing Cα-tetrasubstituted amino acids that are able to form soluble supramolecular structures in water, despite their hydrophobic nature2. Here we present a short alanine (Ala), α-aminoisobutyric acid (Aib) based pentapeptide (Figure 1) that self-assemble into nanostructure having a spherical shape and a diameter around 300-400 nm (DLS results). These nanoassemblies could be exploited to vehiculate in an aqueous environment hydrophobic molecules, using encapsulation approach. As a proof of concept, we selected Curcumin, a polyphenol isolated from the rhizome of Curcuma longa. Curcumin is a fluorescent polyphenol with antioxidant, anti-inflammatory and anti-tumorigenic properties. On the other hand, it shows a very poor bioavailability in vivo, due to its low aqueous solubility and instability, rapid metabolism, and clearance, that definitely limits its use both as a nutraceutical and as a drug. Fluorescence studies on curcumin loaded nanoaggregates show that the molecular interactions between Curcumin and the pentapeptide induce a blue shift and a change in the shape of the emission and absorption peaks of the fluorophore. The nature of these interactions is further being investigated with different techniques in order to demonstrate and explain the encapsulation process of hydrophobic molecules.