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...

Full description

Saved in:
Bibliographic Details
Main Authors: Alessandra Caliendo, Simona Camorani, Luis Exequiel Ibarra, Gabriella Pinto, Lisa Agnello, Sandra Albanese, Antonietta Caianiello, Anna Illiano, Rosaria Festa, Vincenzo Ambrosio, Giosuè Scognamiglio, Monica Cantile, Angela Amoresano, Monica Fedele, Antonella Zannetti, Laura Cerchia
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-08-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001756
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2452-199X