Peptide sequences can be engineered as self-assembling building blocks to produce nanostructures that are biocompatible, reversible, therapeutically active or chemically reactive. This versatility enables the rational design of sequence systems for the preparation of peptide nanobiomaterials with pharmaceutical applications.
Well-defined morphologies such as nanofibers, nanotapes, nanoribbons or nanotubes can reticulate polar solvent matrices, resulting in hydrogels or other solvogels. Such nanostructured gels find direct applications in drug delivery, e.g. as topical or subcutaneous formulations. In this domain, the pioneering example of Lanreotide therapeutic nanostructured hydrogels [1], paved the way to bi-functional peptide sequence engineering. Peptide nanostructured gels can also serve as templates to create nanoporous solid materials, such as peptide-silica aerogels, with applications in drug delivery or wound healing [2].
This talk will report two main families of rationally designed ultrashort sequences: firstly, indolicidin-inspired peptides, designed not only for self-assembly into gel-forming nanostructures [3], but also for concomitant antimicrobial [4-6] and/or anticancer activities. Using biophysical data, in-vitro cell studies and molecular dynamics, we provide insights into sequence-specific activity, formulation and potential mechanisms of action; e.g. cell membrane permeation, potential intracellular targets and the impact of lipid encapsulation on the peptide therapeutic potential. Secondly, tachykinin-inspired peptides will be reported as engineered biotemplates to fabricate composite peptide-silica nanostructures [7] and aerogels, with applications in drug delivery and wound healing. Using biophysical data and nanoscale imaging, the impact of sequence and nanostructure properties on aerogel fabrication will be discussed [2].
1. Valéry, C., et al., Biomimetic organization: Octapeptide self-assembly into nanotubes of viral capsid-like dimension. Proceedings of the National Academy of Sciences, 2003. 100(18): p. 10258-10262.
2. Bakhori, N.M., et al., Emerging Trends in Nanotechnology: Aerogel-Based Materials for Biomedical Applications. Nanomaterials (Basel), 2023. 13(6).
3. Valéry, C., R. Pandey, and J.A. Gerrard, Protein β-interfaces as a generic source of native peptide tectons. Chemical Communications, 2013. 49(27): p. 2825-2827.
4. Cardoso, P., et al., Molecular engineering of antimicrobial peptides: Microbial targets, peptide motifs and translation opportunities. Biophysical reviews, 2021. 13(1): p. 35-69.
5. Cardoso, P., et al., Rational design of potent ultrashort antimicrobial peptides with programmable assembly into nanostructured hydrogels. Frontiers in Chemistry, 2022. 10: p. 1588.
6. Lakic, B., et al., Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides. Journal of Colloid and Interface Science, 2024.
7. Dharmadana, D., et al., Human neuropeptide substance P self-assembles into semi-flexible nanotubes that can be manipulated for nanotechnology. Nanoscale, 2020. 12(44): p. 22680-22687.