Self-assembling peptide-polymer conjugates as promising candidates for drug delivery and imaging

Soft biomaterials based on peptide-polymer conjugates open new horizons for nanomedicine. They are able to self-assemble into nanostructures useful for drug delivery and imaging, 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)2-NH-(CH2-CH2-O)45-CH3 (Pep4-PEG), Cbz-(L-Ala-D-Val)3-NH-(CH2-CH2-O)45-CH3 (Pep6-PEG) are investigated and compared. They were obtained end-linking the proper linear peptide, synthesized via solid-phase peptide synthesis, to a poly(ethylene glycol) chain. The conformational properties of the conjugates and their self-assembling capability were assessed by NMR, CD and fluorescence spectroscopies, DLS, SEM, AFM and TEM microscopies. Finally, the ability of the NPs to encapsulate hydrophobic drugs was evaluated by using curcumin.