DNA Aptamer-Mediated Blood-Brain Barrier Penetration for Targeted Therapeutic Delivery in Glioma

Glioma is one of the most complicated, lethal, and resistant to treatment tumors. A significant problem with Glioma is that the brain is covered with a protective sheet called the blood-brain barrier (BBB),       a barrier of protective cells surrounding the brain. It prevents harmful substances such as toxins and germs from entering and allows nutrients such as oxygen and glucose to enter. However, this prevents essential drugs that may eliminate brain diseases from entering, which can be resolved through aptamers. Aptamers are short, single-stranded molecules of RNA or DNA that can bind to specific targets such as proteins or cells. Aptamers serve as molecular recognition tools, enabling targeted drug delivery across the BBB. We hypothesize that the aptamer binds to the transferrin binding site in the receptor and gets transported across the BBB. AlphaFold3, a software that allows the 3d prediction of a protein’s structure, determined the transferrin receptor structure from its amino acid sequence. UNAfold and FARFAR 2 were used to predict RNA secondary structures and interactions, optimizing aptamer-based therapy de- sign. HDOCK molecular docking identified optimal aptamer-TfR interactions, aiding targeted therapy development and improving receptor-ligand binding insights. The binding energy, which reflects the stability of a nucleus and is equivalent to the energy released during its formation, was calculated using the PDA-Pred tool. The results of the binding energy suggest a strong and thermodynamically favorable interaction between the aptamer and TfR. The aptamer can also bind to the platelet-derived growth factor receptor (PDGFR), preventing the growth factor from activating the receptor. By inhibiting this signaling pathway, the aptamer effectively halts the multiplication of glioma cells, which rely on PDGFR activation for uncontrolled growth. I have incorporated this into my research as well because it poses as an addi- tional therapeutic strategy, aiming to improve treatment effectiveness by disrupting multiple pathways that fuel glioblastoma growth. This research on aptamers seek to create new treatment strategies that improve the precision and effectiveness of therapies for this difficult type of brain cancer.