Electrostatic Targeting of Cancer Cell Membrane Models by NA-CATH:ATRA-1-ATRA-1: A Biophysical Perspective.

Breast cancer continues to be the leading cancer diagnosis among women worldwide, affecting populations in both industrialized and developing regions. Given the rising number of diagnosed cases each year, there is an urgent need to explore novel compounds with potential anticancer properties. One group of such candidates includes cationic peptides, which have shown promise due to their unique membrane-targeting mechanisms that are difficult for cancer cells to resist. This study presents an initial biophysical assessment of NA-CATH:ATRA-1-ATRA-1, a synthetic peptide modeled after NA-CATH, originally sourced from the venom of the Chinese cobra (Naja atra). The peptide's interactions with lipid bilayers mimicking cancerous and healthy cell membranes were examined using differential scanning calorimetry and Fourier-transform infrared spectroscopy. Findings revealed a pronounced affinity of NA-CATH:ATRA-1-ATRA-1 for eukaryotic membrane lipids, particularly phosphatidylserine, indicating that its mechanism likely involves electrostatic attraction to negatively charged lipids characteristic of cancer cell membranes. Such biophysical insights are vital for understanding how membrane-active peptides could be harnessed in future cancer therapies.