A Membrane-Retained DNA Aptamer Promotes Intracellular Platinum Accumulation and Chemosensitization in Ovarian Cancer

Cisplatin resistance remains a major obstacle in the effective treatment of ovarian cancer. Here, we report a membrane-retained DNA aptamer, DR-A2, discovered via Cell-SELEX using cisplatin-resistant ovarian cancer cells as the selection target. DR-A2 exhibited high affinity and specificity toward drug-resistant ovarian cancer cells and their secreted exosomes, while showing negligible binding to drug-sensitive parental cells or normal epithelial cells. Mechanistic studies revealed that DR-A2 increases intracellular cisplatin retention in resistant cells. In vivo, DR-A2 preferentially accumulated in cisplatin-resistant xenografts and significantly boosted the antitumor efficacy of cisplatin without causing systemic toxicity. These results validate DR-A2 as a bifunctional aptamer capable of both selective tumor recognition and chemosensitization, offering a promising strategy to overcome platinum resistance in ovarian cancer.