Volume 64, Issue 24 e202425252

Research Article

DNA Framework-Ensembled Aptamers Enhance Fluid Stability in Circulating Tumor Cells Capture for Tumor Treatment Evaluation

Yirong Chen

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Dr. Fan Li,

Dr. Fan Li

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Shuyang Zhang,

Shuyang Zhang

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Feng Liu,

Feng Liu

Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Chenzhou Mao,

Chenzhou Mao

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Min Li,

Dr. Min Li

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Jinhua Jiang,

Corresponding Author

Dr. Jinhua Jiang

[email protected]

Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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Dr. Yueyue Zhang,

Corresponding Author

Dr. Yueyue Zhang

[email protected]

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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Prof. Chunhai Fan,

Prof. Chunhai Fan

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China

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Prof. Xiaolei Zuo,

Corresponding Author

Prof. Xiaolei Zuo

[email protected]

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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Yirong Chen,

Yirong Chen

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Dr. Fan Li,

Dr. Fan Li

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Shuyang Zhang,

Shuyang Zhang

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

These authors contributed equally to this work.

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Feng Liu,

Feng Liu

Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Chenzhou Mao,

Chenzhou Mao

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Min Li,

Dr. Min Li

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Dr. Jinhua Jiang,

Corresponding Author

Dr. Jinhua Jiang

[email protected]

Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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Dr. Yueyue Zhang,

Corresponding Author

Dr. Yueyue Zhang

[email protected]

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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Prof. Chunhai Fan,

Prof. Chunhai Fan

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

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Prof. Xiaolei Zuo,

Corresponding Author

Prof. Xiaolei Zuo

[email protected]

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China

E-mail: [email protected], [email protected], [email protected]

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First published: 05 March 2025

https://doi.org/10.1002/anie.202425252

Citations: 1

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Graphical Abstract

We develop a tetrahedral DNA framework (TDF) engineered multivalent aptamers (TEA_n) with programmable ligands size and configuration, enabling high-efficiency capture of CTCs and accurate monitoring of clinical treatment progress. The precisely structured TEA_n ensures the size-matching and cooperative hybridization with epithelial cell adhesion molecule (EpCAM) clusters on cell membrane.

Abstract

The recognition and binding via receptor-ligand interactions on cell membranes often weaken in complex environments, such as whole blood samples from cancer patients, making disease diagnosis and treatment evaluation unfavorable. Constructing multivalent ligands with sufficient fluid stability in complex environments remains a challenge. Herein, we develop a tetrahedral DNA framework (TDF) ensembled multivalent aptamers (TEA_n, n = 1–3) with programmable ligands size, enabling efficient capture of circulating tumor cells (CTCs) and accurate monitoring of clinical treatment progress. The precisely structured TEA_n ensures the size-matching and cooperative hybridization with epithelial cell adhesion molecule (EpCAM) on cell membrane. Compared to traditional aptamer approach, the dissociation constants (K_d) of TEA₃ exhibits ∼20-fold growth in serum due to its precise size and rigid DNA framework. This high-affinity interaction significantly enhances capture efficiency by improving fluid stability of TEA_n and magnetic beads complex in complex environment. In addition, this CTC detection strategy is applied for clinical tumor treatment evaluation and progress monitoring in liver cancer patient samples, achieving an accuracy of ∼83.3% in classifying patients as complete or partial responses (CR/PR). Overall, this strategy will strongly promote potential clinical application of DNA framework for cancer diagnosis and disease progression monitoring.

Conflict of Interests

The authors declare no conflict of interest.

Open Research

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

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Volume64, Issue24

June 10, 2025

e202425252

DNA Framework-Ensembled Aptamers Enhance Fluid Stability in Circulating Tumor Cells Capture for Tumor Treatment Evaluation

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Abstract

Conflict of Interests

Open Research

Data Availability Statement

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DNA Framework-Ensembled Aptamers Enhance Fluid Stability in Circulating Tumor Cells Capture for Tumor Treatment Evaluation

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Outside Back Cover: DNA Framework-Ensembled Aptamers Enhance Fluid Stability in Circulating Tumor Cells Capture for Tumor Treatment Evaluation (Angew. Chem. Int. Ed. 15/2025)

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Abstract

Conflict of Interests

Open Research

Data Availability Statement

Supporting Information

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