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Zwitterionic microgel preservation platform for circulating tumor cells in whole blood specimen

Author

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  • Yiming Ma

    (Tianjin University)

  • Jun Zhang

    (Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital)

  • Yunqing Tian

    (Tianjin University)

  • Yihao Fu

    (Tianjin University)

  • Shu Tian

    (Tianjin University)

  • Qingsi Li

    (Tianjin University)

  • Jing Yang

    (Tianjin University)

  • Lei Zhang

    (Tianjin University)

Abstract

The immediate processing of whole blood specimen is required in circulating tumor cell-based liquid biopsy. Reliable blood specimen stabilization towards preserving circulating tumor cells can enable more extensive geographic sharing for precise rare-cell technology, but remains challenging due to the fragility and rarity of circulating tumor cells. Herein, we establish a zwitterionic magnetic microgel platform to stabilize whole blood specimen for long-term hypothermic preservation of model circulating tumor cells. We show in a cohort study of 20 cancer patients that blood samples can be preserved for up to 7 days without compromising circulating tumor cell viability and RNA integrity, thereby doubling the viable preservation duration. We demonstrate that the 7-day microgel-preserved blood specimen is able to reliably detect cancer-specific transcripts, similar to fresh blood specimens, while there are up/down expression regulation of 1243 genes in model circulating tumor cells that are preserved by commercial protectant. Mechanistically, we find that the zwitterionic microgel assembly counters the cold-induced excessive reactive oxygen species and platelet activation, as well as extracellular matrix loss-induced cell anoikis, to prevent circulating tumor cell loss in the whole blood sample. The present work could prove useful for the development of blood-based noninvasive diagnostics.

Suggested Citation

  • Yiming Ma & Jun Zhang & Yunqing Tian & Yihao Fu & Shu Tian & Qingsi Li & Jing Yang & Lei Zhang, 2023. "Zwitterionic microgel preservation platform for circulating tumor cells in whole blood specimen," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40668-1
    DOI: 10.1038/s41467-023-40668-1
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    References listed on IDEAS

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    1. Caroline I. Biggs & Trisha L. Bailey & Graham & Christopher Stubbs & Alice Fayter & Matthew I. Gibson, 2017. "Polymer mimics of biomacromolecular antifreezes," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    2. Mert Boya & Tevhide Ozkaya-Ahmadov & Brandi E. Swain & Chia-Heng Chu & Norh Asmare & Ozgun Civelekoglu & Ruxiu Liu & Dohwan Lee & Sherry Tobia & Shweta Biliya & L. DeEtte McDonald & Bassel Nazha & Ome, 2022. "High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Sunitha Nagrath & Lecia V. Sequist & Shyamala Maheswaran & Daphne W. Bell & Daniel Irimia & Lindsey Ulkus & Matthew R. Smith & Eunice L. Kwak & Subba Digumarthy & Alona Muzikansky & Paula Ryan & Ulyss, 2007. "Isolation of rare circulating tumour cells in cancer patients by microchip technology," Nature, Nature, vol. 450(7173), pages 1235-1239, December.
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    Cited by:

    1. Xihao Pan & Rui Li & Wenyue Li & Wei Sun & Yiyang Yan & Xiaochen Xiang & Jinghua Fang & Youguo Liao & Chang Xie & Xiaozhao Wang & Youzhi Cai & Xudong Yao & Hongwei Ouyang, 2024. "Silk fibroin hydrogel adhesive enables sealed-tight reconstruction of meniscus tears," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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