PDGF-mimicking Supramolecular Nanofibers for Ionizing Radiation-induced Injury Repair

Abstract Platelet-derived growth factors (PDGFs) play crucial roles in regulating cell proliferation, apoptosis, and migration and have been recommended for injury repair in clinical practice. However, the low stability, poor biological barrier penetration ability, and high cost of protein drugs hinders their wide application. The development of small molecules or nanomaterials capable of simulating the bioactivity of PDGFs may overcome the shortcomings of PDGF proteins and expand their application. Herein, we report the first supramolecular nanofiber of the self-assembling peptide Nap-FFGVRKKP (Compound 1) with superior bioactivity over the PDGF protein. The peptide derivative Nap-FFG formed a β-sheet conformation, which mimicks the four-β-sheet peptide in PDGF, and the pentapeptide VRKKP from loop 3 in PDGF that is crucial for binding with the PDGF receptor. Therefore, the nanofibers possessed the multivalent loop 3 peptide on the surface that might assist oligomerization and activation of the PDGF receptor. The results indicated that our nanomaterials efficiently activated the PDGF signaling pathway and promoted NIH 3T3 cell proliferation and migration. Moreover, they significantly reduced the apoptosis rate caused by 10 Gy X-ray radiation from 33.60% to 5.83% and showed a good therapeutic effect on the ionizing radiation-induced injury repair by reducing the inflammatory response and enhancing skin regeneration. Our study offers a versatile strategy to construct nanomaterials with enhanced biological activity through multivalent interactions, and the development of PDGF mimics may overcome the limitation of PDGFs for their applications in injury repair, cell culture, cosmetics, and regenerative medicine.