Aggression to Biomembranes by Hydrophobic Tail Chains under the Stimulus of Reductant

Stimulus-responsive materials hold significant promise for antitumor applications due to their variable structures and physical properties. In this paper, a series of peptides with a responsive viologen derivative, Pep-C_nV (n = 1, 2, 3) were designed and synthesized. The process and mechanism of the interaction were studied and discussed. An ultraviolet-visible (UV) spectrophotometer and fluorescence spectrophotometer were used to study their redox responsiveness. Additionally, their secondary structures were measured by Circular Dichroism (CD) in the presence or absence of the reductant, Na₂SO₃. DPPC and DPPG liposomes were prepared to mimic normal and tumor cell membranes. The interaction between Pep-C_nV and biomembranes was investigated by the measurements of surface tension and cargo leakage. Results proved Pep-C_nV was more likely to interact with the DPPG liposome and destroy its biomembrane under the stimulus of the reductant. And the destruction increased with the length of the hydrophobic tail chain. Pep-C_nV showed its potential as an intelligent antitumor agent.