Self-assembling amphiphilic peptides: A novel approach to create new drug systems and three-dimensional scaffolds for tissue regeneration. A resourceful mine not yet fully explored.

摘要

Molecular self-assembly offers unique features for the development of novel supramolecular structures and advanced materials. The inspiration for the creation of these complex structures is often driven by nature, where complex architectures are obtained from simple building block such as amino acids, nucleic acids and lipids.Peptide-based nanostructures constitute a novel route to create well organized self-assembled materials that eventually can be used in a variety of different fields. They can be divided in different classes based on the architecture of the overall molecule. My research is mainly focused on two types of peptide-based structures: peptide amphiphiles, in which an amino acidic sequence is tailed with an hydrophobic molecule, such as palmitic acid, and facially amphiphilic peptides, which is made by proper sequence patterning of hydrophobic and hydrophilic amino acids.In chapter 2 I describe how a peptide amphiphile was designed, synthesized and tested on different types of cancer cell lines, and it proved to be effective in reducing the growth of malignant cells. This peptide works as an inhibitor of the HOX-PBX1 interaction. HOX and PBX I are two transcription factors that are deeply involved in the DNA regulation during embryogenesis and they are found to be highly miss-regulated in several types of cancers. Until now, peptide amphiphiles have been used mostly as drug carriers. This work constitutes one of the first studies in which a peptide amphiphile molecule can work both as a drug and as a drug carrier, simultaneously.3D-scaffolds for tissue engineering applications are another hot area in which self-assembling peptides are finding several applications. Driven by this motivation, chapter 3, 4 and 5 describe how I designed, synthesized and investigated the properties of a new class of facial peptide amphiphile. These peptides, when dissolved in an aqueous environment and under the right pH and salt conditions, have proven to quickly self-assemble in long and entangled nanofibers that ultimately form stable hydrogels. These hydrogels have potential applications as bio-scaffolds for tissue regeneration, as cells are entrapped in their network. The mechanical properties of these hydrogels can be triggered using different approaches and it is possible to obtain very strong materials, even at very low concentrations of the peptide, such as 1% by weight.In order to be safely used for bio-applications, hydrogel materials must be need to have two main features: biocompatibility and biodegradability. The hydrogels obtained through self-assembling peptides have proven to be both biocompatible and biodegradable, thanks to the introduction of a short amino acid sequence recognized by proteases, which is described in chapter 5.In conclusions, the results collected in this study show how a simple building block, such as a small peptide, can serve as an extremely powerful and flexible tool to design complex self-assembled systems. This is area of research is indeed full of potential that has not yet been completely explored.