Synthesis, characterization, and exosomal corona formation of self-assembled dipeptide nanomaterials

Exosomes (Exos), also known as small extracellular vesicles, are naturally occurring nanoparticles (NPs), which are characterized by their nanometer size and negative charged in physiological environments. While it is widely accepted that proteins and biological compounds adhere to different nanomaterials (NMs), forming an outer layer known as the biomolecule corona (BC), the detailed understanding of factors contributing to BC formation as well as of its biological effects remains limited. Studies have shown that BC formation can affect the physicochemical properties of synthetic and natural NPs once contacting biological fluids. Here, we present a study investigating the novel concept of exosomal corona formation, which in contrast to the well-documented BC mainly consists of Exos/exosomal components. For this purpose, peptide-based Fmoc-Lysine (Fmoc-Lys) NMs were synthesized and characterized, and interaction studies with (cancer) cell-derived Exos were performed. Measurements of size, zeta potential, and colloidal stability indicate exosomal corona formation. Furthermore, cell viability experiments showed that the Exo-NM interaction resulted in reduced nanotoxicity profile indicating practical relevance for biological applications of these NMs. In summary, here we provide first evidence supporting the concept of exosomal corona formation around NMs that should become part of evaluating interactions at nano-bio-interfaces.