Novel Aptamer-Drug Conjugate for Targeted Therapy in Triple-Negative Breast Cancer

  • J Med Chem. 2025 Jul 20. doi: 10.1021/acs.jmedchem.5c00492.
Feng Xu  1 ,  Jingtong Xu  1 ,  Feng Han  2  3 ,  Ke Wang  1 ,  Fulong Wang  3 ,  Hanyang Yu  3 ,  Xiaoxiang Guan  1  4
Affiliations
  • 1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 2. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, Jiangsu 210023, China.
  • 3. State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, Jiangsu 210023, China.
  • 4. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 210029, China.
PMID: 40685636 DOI: 10.1021/acs.jmedchem.5c00492
Abstract

Triple-negative breast Cancer (TNBC) is a highly aggressive malignancy lacking targeted therapeutic modalities. Aptamers are promising targeting agents with high specificity and affinity. In this study, we identified a chemically modified nucleic acid aptamer (AptT1) that specifically recognized and internalized into TNBC cells. Mechanistic studies revealed that AnxA2 was an essential protein in facilitating AptT1 internalization via clathrin-mediated endocytosis. Furthermore, we constructed an aptamer-drug conjugate (ApDC) to selectively deliver a cytotoxic agent (SN38) to TNBC cells and demonstrated significant efficacy and safety in a TNBC xenograft model. These findings suggest that AptT1-based ApDC holds great potential as an innovative targeted strategy for TNBC.

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