Computational Simulations of Bispecific Aptamer Targeting EpCAM and Transferrin Receptors for Treating Brain Cancer Metastases

Secondary brain tumors, or brain metastases, occur when cancer cells spread from other parts of the body to the brain. These brain disorders are challenging to treat since the blood-brain barrier inhibits most small molecules and other therapeutic agents from entering the brain. Aptamers are small segments of single-stranded nucleotides that specifically bind to a target biomolecule and are gaining popularity in diagnostics, therapeutics, and biosensing. Recently, bispecific aptamers have been designed to cross the BBB (by binding the transferrin receptor) and interact with the target cancer cell (via the EpCAM receptor). We hypothesize that the bifunctional nature of the aptamer could be due to the nucleotide conformations that bind to both the receptors. In our investigation, we have performed molecular docking simulations on both receptors. In total, nine aptamers were modeled using the Vfold2D and Vfold3D software. The obtained 3D structures of aptamers were docked on the two receptors to understand the receptor-aptamer binding interaction. These structures were analyzed by computing the aptamer interactions and visual inspection which shows that aptamer TENP binds strongly to the transferrin and EpCAM receptors. The current work can potentially improve drug delivery across the blood-brain barrier, paving the way for future advancements in cancer therapeutics and personalized medicine.

Keywords: Bispecific aptamers, Transferrin receptor, EpCAM, Brain Cancer Metastases.