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...

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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
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001756
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author 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
author_facet 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
author_sort Alessandra Caliendo
collection DOAJ
description 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.
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spelling doaj-art-bdf1a82a8f0942d19b8a39da110b77e72025-08-20T03:20:16ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-08-015044346010.1016/j.bioactmat.2025.04.027A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growthAlessandra Caliendo0Simona Camorani1Luis Exequiel Ibarra2Gabriella Pinto3Lisa Agnello4Sandra Albanese5Antonietta Caianiello6Anna Illiano7Rosaria Festa8Vincenzo Ambrosio9Giosuè Scognamiglio10Monica Cantile11Angela Amoresano12Monica Fedele13Antonella Zannetti14Laura Cerchia15Institute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitute of Environmental Biotechnology and Health (INBIAS), National University of Rio Cuarto (UNRC), National Council for Scientific and Technological Research (CONICET), Río Cuarto, X5800BIA, ArgentinaDipartimento di Scienze Chimiche Università di Napoli Federico II, Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi, Roma, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitute of Biostructures and Bioimaging, National Research Council, 80145, Naples, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyDipartimento di Scienze Chimiche Università di Napoli Federico II, Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi, Roma, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitutional Biobank-Scientific Directorate, National Cancer Institute INT-IRCCS Fondazione G. Pascale, 80131, Naples, ItalyInstitutional Biobank-Scientific Directorate, National Cancer Institute INT-IRCCS Fondazione G. Pascale, 80131, Naples, ItalyDipartimento di Scienze Chimiche Università di Napoli Federico II, Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi, Roma, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, ItalyInstitute of Biostructures and Bioimaging, National Research Council, 80145, Naples, ItalyInstitute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, 80131, Naples, Italy; Corresponding author. Institute of Endotypes in Oncology, Metabolism and Immunology ''Gaetano Salvatore'', National Research Council, Italy.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.http://www.sciencedirect.com/science/article/pii/S2452199X25001756AptamerCD44Chemoresistant triple-negative breast cancerBiomarker identificationTargeted cancer therapy
spellingShingle 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
A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
Bioactive Materials
Aptamer
CD44
Chemoresistant triple-negative breast cancer
Biomarker identification
Targeted cancer therapy
title A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
title_full A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
title_fullStr A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
title_full_unstemmed A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
title_short A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth
title_sort novel cd44 targeting aptamer recognizes chemoresistant mesenchymal stem like tnbc cells and inhibits tumor growth
topic Aptamer
CD44
Chemoresistant triple-negative breast cancer
Biomarker identification
Targeted cancer therapy
url http://www.sciencedirect.com/science/article/pii/S2452199X25001756
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