A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
Triple-negative breast cancer (TNBC) represents a significant therapeutic challenge owing to the scarcity of targeted medicines and elevated recurrence rates. We previously reported the development of the nuclease-resistant RNA sTN58 aptamer, which selectively targets TNBC cells. Here, sTN58 aptamer was employed to capture and purify its binding target from the membrane protein fraction of cisplatin-resistant mesenchymal stem-like TNBC cells. Mass spectrometry in conjunction with aptamer binding assays across various cancer cell lines identified CD44 as the cellular target of sTN58. By binding to CD44, sTN58 inhibits the invasive growth and hyaluronic acid-dependent tube formation in chemoresistant TNBC cells, where CD44 serves as a key driver of tumor cell aggressiveness and stem-like plasticity. Moreover, in vivo studies demonstrated the aptamer's high tumor targeting efficacy and its capacity to significantly inhibit tumor growth and lung metastases following intravenous administration in mice with orthotopic TNBC. Overall, our findings reveal the striking potential of sTN58 as a targeting reagent for the recognition and therapy of cancers overexpressing CD44.
Authors
- Gabriella Pinto (ORCID: https://orcid.org/0000-0001-9169-3452)
- Monica Cantile (ORCID: https://orcid.org/0000-0001-7840-3369)
- Laura Cerchia (ORCID: https://orcid.org/0000-0002-7633-7932)
- Simona Camorani (ORCID: https://orcid.org/0000-0003-1144-0485)
- Angela Amoresano (ORCID: https://orcid.org/0000-0002-8386-655X)
- Lisa Agnello (ORCID: https://orcid.org/0000-0001-5923-1987)
- Monica Fedele (ORCID: https://orcid.org/0000-0002-9171-1312)
- Giosuè Scognamiglio (ORCID: https://orcid.org/0000-0003-4376-111X)
- Anna Illiano (ORCID: https://orcid.org/0000-0003-1491-8966)
- Sandra Albanese (ORCID: https://orcid.org/0000-0002-7112-273X)
- Antonella Zannetti (ORCID: https://orcid.org/0000-0002-6753-3659)
- Vincenzo Ambrosio (ORCID: https://orcid.org/0000-0003-3439-1428)
- Luis Exequiel Ibarra (ORCID: https://orcid.org/0000-0002-6077-7992)
- Alessandra Caliendo (ORCID: https://orcid.org/0009-0001-2506-513X)
- Rosaria Festa
- Antonietta Caianiello
Institutions
- Universidad Nacional de Río Cuarto (AR)
- Institute of Biostructure and Bioimaging (IT)
- Institute for Experimental Endocrinology and Oncology (IT)
- Istituto Nazionale Biostrutture e Biosistemi (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- National Research Council (IT)
Publication Details
- Journal
- Bioactive Materials
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1016/j.bioactmat.2025.04.027
- Citations
- 4
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 3.22