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Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping

Author

Listed:
  • Hui-Da Li

    (Northeastern University)

  • Yuan-Qiang Chen

    (Soochow University)

  • Yan Li

    (Zhejiang University)

  • Xing Wei

    (Northeastern University)

  • Si-Yi Wang

    (Northeastern University)

  • Ying Cao

    (Northeastern University)

  • Rui Wang

    (Northeastern University)

  • Cong Wang

    (Cancer Hospital of China Medical University)

  • Jing-Yue Li

    (Cancer Hospital of China Medical University)

  • Jian-Yi Li

    (Cancer Hospital of China Medical University)

  • Hong-Ming Ding

    (Soochow University)

  • Ting Yang

    (Northeastern University)

  • Jian-Hua Wang

    (Northeastern University)

  • Chuanbin Mao

    (The Chinese University of Hong Kong)

Abstract

The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

Suggested Citation

  • Hui-Da Li & Yuan-Qiang Chen & Yan Li & Xing Wei & Si-Yi Wang & Ying Cao & Rui Wang & Cong Wang & Jing-Yue Li & Jian-Yi Li & Hong-Ming Ding & Ting Yang & Jian-Hua Wang & Chuanbin Mao, 2024. "Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50064-y
    DOI: 10.1038/s41467-024-50064-y
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    1. Brieuc Van Nieuwenhuyse & Dimitri Van der Linden & Olga Chatzis & Cédric Lood & Jeroen Wagemans & Rob Lavigne & Kaat Schroven & Jan Paeshuyse & Catherine de Magnée & Etienne Sokal & Xavier Stéphenne &, 2022. "Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Jin-Woo Oh & Woo-Jae Chung & Kwang Heo & Hyo-Eon Jin & Byung Yang Lee & Eddie Wang & Chris Zueger & Winnie Wong & Joel Meyer & Chuntae Kim & So-Young Lee & Won-Geun Kim & Marcin Zemla & Manfred Auer &, 2014. "Biomimetic virus-based colourimetric sensors," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    3. Stefka Tyanova & Reidar Albrechtsen & Pauliina Kronqvist & Juergen Cox & Matthias Mann & Tamar Geiger, 2016. "Proteomic maps of breast cancer subtypes," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
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