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

Yiming Ma, Jun Zhang, Yunqing Tian, Yihao Fu, Shu Tian, Qingsi Li, Jing Yang () and Lei Zhang ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40668-1

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