Harnessing Mirror Image Peptides: nanovector for Nucleic Acids delivery in cancer treatment

The development of efficient delivery systems for nucleic acid-based cancer therapies is an ongoing challenge. Peptide-based systems are emerging as promising strategy due to their tunable properties. Nevertheless, their clinical application is hindered by susceptibility to proteases and limited stability. In this project, we investigate the potential of D-peptides, protease-resistant synthetic peptides composed exclusively of D-amino acids (MIPs, Mirror-Image Peptides), as nanovectors for nucleic acid delivery. Due to their inverted chirality, D-peptides demonstrate remarkable resistance to protease activity while retaining biological functionality. Among various constructs, we selected a promising sequence characterized by the presence of charged amino acids, which enable self-assembling and the complexation of negatively charged nucleic acids (NAs). Using an automated microfluidic-based synthesis we produce nanoparticles complexed with either RNA or double-stranded DNA.