Diethylene glycol functionalized self-assembling peptide nanofibers and their hydrophobic drug delivery potential.
Self-assembling peptide nanofibers have emerged as important nanobiomaterials, with such applications as delivery of therapeutic agents and vaccines, nanofabrication and biomineralization, tissue engineering and regenerative medicine. Recently a new class of self-assembling peptides has been introduced, which takes into consideration amino acid pairing (AAP) strategies in the peptide sequence design. Even though these peptides have shown promising potential in the design of novel functional biomaterials, they have a propensity to initiate uncontrollable aggregation and be degraded by proteolytic enzymes. These present the most significant challenge in advancing self-assembling peptides for in vitro and in vivo applications. Functionalizing biomaterials with polyethylene glycol (PEG) has been shown to surmount such problems. Here the results of conjugating diethylene glycol (DEG), a short segment of PEG, to one of the AAP peptides, AAP8, with eight amino acids in sequence, are reported. The results indicate that incorporation of DEG into the peptide sequence modulates fiber self-assembly through creating more aligned and uniform nanostructures. This is associated with increasing solubility, stability, and secondary structure β-sheet content of the peptide. The DEG conjugate of AAP8 also shows reduced cellular cytotoxicity. Functionalization of AAP8 improves the capability of the peptide to stabilize and deliver a hydrophobic anticancer compound, ellipticine, in aqueous solution, consequently inducing greater cytotoxicity to lung carcinoma cells over a relatively long time, compared with non-functionalized AAP8. The presented functionalized peptide and its drug delivery application indicate a potentially useful design strategy for novel self-assembling peptide biomaterials for biotechnology and nanomedicine.
Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Parisa
P
Sadatmousavi
Tewodros
T
Mamo
P
P
Chen
D002942:Circular Dichroism; D016503:Drug Delivery Systems; D005026:Ethylene Glycols / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D057139:Nanofibers; D010455:Peptides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
D005026:Ethylene Glycols; D010455:Peptides; C013484:diethylene glycol