In this work, an integrated biophysical and biological study is presented describing both the structural and biological features of the novel peptide AVPDVAFNAYG (BD11) and its conjugate with an adamantanyl portion (Ada-(PEG)4-BD11) forming supramolecular assemblies with the water-soluble β-CD polymer SuBCDPS. Interestingly, BD11 and SuBCDPS did not affect the viability of either HDF or MDA-MB-231 BC cells, indicating good biocompatibility. In contrast, the SuBCDPS/Ada-(PEG)4-BD11 complex reduced cell migration in both cell lines, with a significant inhibitory effect at the highest concentration. Importantly, this reduction in migration occurred in the absence of cytotoxicity, indicating that the complex modulates cell motility without impairing cell viability. This effect is particularly relevant in MDA-MB-231 cells, which are highly invasive and represent a model of aggressive triple-negative breast cancer. In HDF cells, the SuBCDPS/Ada-(PEG)4-BD11 complex reduced cell migration compared to untreated controls, although no significant difference was observed when compared with SuBCDPS alone. This suggests that in normal fibroblasts, the inhibitory effect may partially derive from the delivery system itself. In contrast, in MDA-MB-231 cells a significant difference was detected between SuBCDPS and SuBCDPS/Ada-(PEG)4-BD11, indicating that the peptide–conjugated complex exerts a specific anti-migratory effect in the cancer cell context. However, the anti-migratory effect of free SuBCDPS on cancer cell lines is relevant and worth further investigation.
Synthetic route for the preparation of 6-deoxy-6-(2-carboxyethyl)thio-β-CD polymer crosslinked with epichlorohydrin (SuBCDPS), (nave≅6) corresponding to a DS = 6.06.
Reference
Rita Turnaturi, Giuseppa Augello, Giuseppe Nocito, Marcello Tagliavia, Stefania Zimbone, Rosalia Pellitteri, Giuseppina Sabatino, Giuseppe Di Natale, Michele F. M. Sciacca,| Milo Malanga, Antonino Mazzaglia, Melchiorre Cervello, Giuseppe Pappalardo (2026) Structural Characterization, β-Cyclodextrin Polymer Interaction, and Biological Assessment of the N-Terminal Peptide from the RPD-1 Big Defensin of Ruditapes philippinarum. Chemistry – Methods, 6:e202500158. https://doi.org/10.1002/cmtd.202500158