Self-assembling octapeptide-polymer conjugates as promising candidates for drug delivery

Soft biomaterials based on peptide-polymer conjugates open new horizons for nanomedicine. They are able to self-assemble into nanostructures useful for drug delivery, the properties of which can be finely tuned at nanometer scale. Among the strategies developed for peptide engineering, those characterized by regularly alternating enantiomeric sequences are particularly attractive, since they provide low-pitch helices that self-assemble in stacks directed and stabilized by hydrogen bonds where the peripheral side chains, are available to be functionalized with various molecules, such as polymers. When the peptide and polymer are suitably chosen in order to achieve core-shell morphology, these conjugates are able to self-assemble in water in stable nanoparticles (NPs) with enhanced circulation half-life. Herein, the self-assembling properties of the hybrid conjugates Cbz-(L-Ala-D-Val)4-NH-(CH2-CH2-O)45-CH3 (Pep8-PEG) and For-(D-Phe-L-Cys(Acm))4-NH-(CH2-CH2-O)45-CH3 (Pep8Phe-PEG) are investigated and compared. The structural properties of NPs formed for self-assembling of the conjugates were assessed by NMR, CD and fluorescence spectroscopies, DLS, and TEM microscopies.