Advancing Targeted Combination Chemotherapy in Triple Negative Breast Cancer: Nucleolin Aptamer-Mediated Controlled Drug Release

Abstract Triple negative breast cancer (TNBC) poses a significant challenge due to its aggressive nature and limited treatment options. While scheduled treatment with paclitaxel and fluorouracil has shown efficacy, their uncontrolled distribution remains challenging. To address this issue, we designed a dual chemo-loaded aptamer with redox-sensitive caged paclitaxel for rapid release and non-cleavable caged fluorouracil for slow release. The nucleolin aptamer significantly improved tumor-targeting, enhancing the effectiveness of the conjugated drugs in TNBC cells. Through nucleolin-mediated endocytosis, the drugs achieved scheduled release, resulting in improved antitumor activity and reduced toxicity in vitro and in vivo. These findings offer new possibilities for developing targeted combination chemotherapy in TNBC.