摘要:SummaryTriple-negative breast cancer (TNBC) is a high heterogeneous group of tumors with a distinctly aggressive nature and high rates of relapse. So far, the lack of any known targetable proteins has not allowed a specific anti-tumor treatment. Therefore, the identification of novel agents for specific TNBC targeting and treatment is desperately needed. Here, by integrating cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) for the specific recognition of TNBC cells with high-throughput sequencing technology, we identified a panel of 2′-fluoropyrimidine-RNA aptamers binding to TNBC cells and their cisplatin- and doxorubicin-resistant derivatives at low nanomolar affinity. These aptamers distinguish TNBC cells from both non-malignant and non-TNBC breast cancer cells and are able to differentiate TNBC histological specimens. Importantly, they inhibit TNBC cell capacity of growingin vitroas mammospheres, indicating they could also act as anti-tumor agents. Therefore, our newly identified aptamers are a valuable tool for selectively dealing with TNBC.Graphical AbstractDisplay OmittedHighlights•Six 2′FPy-RNA aptamers were obtained by TNBC Cell-SELEX/NGS•They distinguish TNBC cells from non-malignant and non-TNBC breast cancer cells•They differentiate TNBC histological specimens by aptamer-based staining•They inhibit TNBC cell lines capacity of growingin vitroas mammospheresBiochemistry; Cell Biology; Cancer