Aptamer-based strategies for glioblastoma: From SELEX to preclinical success

Glioblastoma presents a persistent therapeutic challenge due to extensive intratumoral heterogeneity and the blood-brain barrier. Nucleic acid aptamers offer an effective alternative to overcome these physiological obstacles where conventional modalities often have limited success. This review outlines the progression of aptamers from basic ligands to functional therapeutics, with a focus on targeting glioblastoma stem cells and engineering mechanisms for blood-brain barrier traversal. We discuss how recent biotechnological developments, including Cell-SELEX and AI-supported design, are solving earlier issues related to in vivo stability and conformational selectivity. Additionally, the article evaluates the shift toward multifunctional systems such as aptamer-drug conjugates and "drugtamers" designed for receptor-mediated transport. These advances indicate that next-generation aptamer platforms may overcome current translational limitations and enable more precise neuro-oncological treatments.