Novel self-assembling cyclic peptides with reversible supramolecular nanostructures

Self-assembly peptides (SAPs) are an important class of hydrogels used in nanomedicine for tissue repair and neural regeneration. Due to their unique properties, SAPs may be used in a wide range of applications but some limitations, such as low bioavailability and rapid hydrolysis degradation, need to be overcome. Here, we describe the synthesis and characterization of two novel cyclic SAPs without the use of d/l-alternating amino acids, showing a reversible transition of their supramolecular nanostructures, from nanotubes/nanofibers into nanovesicles/nanospheres. The investigation, characterization and optimization are performed using atomic force microscopy (AFM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, Raman analysis, circular dichroism (CD), and rheology measurements. Also, in vitro cell viability assays show negligible toxicity of the representative optimized cyclic SAP towards human neural stem cells (hNSCs). Our results suggest that linear SAP theoretical background can be applied to develop cyclic SAPs, with important implications in the scalable fabrication of inter-changeable nanostructures, as well as for biomedical applications, including tissue regeneration, drug-delivery, drug-design, sensing, imaging, and size selectivity.