Abstract
Circulating tumor cells (CTCs) are a type of cancer cells that circulate in the peripheral blood after breaking away from solid tumors and are essential for the establishment of distant metastasis. Up to 90% of cancer-related deaths are caused by metastatic cancer. As a new type of liquid biopsy, detecting and analyzing CTCs will provide insightful information for cancer diagnosis, especially the in-time disease status, which would avoid some flaws and limitations of invasive tissue biopsy. However, due to the extremely low levels of CTCs among a large number of hematologic cells, choosing immunocapture platforms for CTC detection and isolation will achieve good performance with high purity, selectivity, and viability. These properties are directly associated with precise downstream analysis of CTC profiling. Recently, inspired by the nanoscale interactions of cells in the tissue microenvironment, platforms based on nanomaterials have been widely explored to efficiently enrich and sensitively detect CTCs. In this review, various immunocapture platforms based on different nanomaterials for efficient isolation and sensitive detection of CTCs are outlined and discussed. First, the design principles of immunoaffinity nanomaterials are introduced in detail. Second, the immunocapture and release of platforms based on nanomaterials ranging from nanoparticles, nanostructured substrates, and immunoaffinity microfluidic chips are summarized. Third, recent advances in single-cell release and analysis of CTCs are introduced. Finally, some perspectives and challenges are provided in future trends of CTC studies.
Highlights
The International Agency for Research on Cancer provided the cancer incidence and mortality in 2020, based on Global Cancer Statistics 2020 (Sung et al, 2021)
The concept of circulating tumor cells (CTCs) was proposed, these cells refer to all kinds of tumor cells that shed from cancerous tumors and enter the peripheral blood system, and they may have the ability to develop at other tumor sites and have important relationships with metastasis (Chaffer and Weinberg, 2011; Alix-Panabières and Pantel, 2013)
Downstream molecular analysis of isolated CTCs from 11 breast cancer patients was demonstrated, and the results showed that the contents of 5-methyl-2ʹ-deoxycytidine in CTCs of breast cancer patients are lower than those of healthy controls, which made this HZnPNS platform promising for personal cancer therapy
Summary
The International Agency for Research on Cancer provided the cancer incidence and mortality in 2020, based on Global Cancer Statistics 2020 (Sung et al, 2021). Because tumor cells are usually larger than RBCs, and the high nucleo-cytoplasmic ratio (N/C ratio) of tumor cells causes the overall biomechanical properties of cancerous cells to differ from those of WBCs, CTC isolations based on the size (Hayata et al, 2010; Huang et al, 2014), deformability (Beech et al, 2012), density (Kim et al, 2014), or dielectric properties (Shim et al, 2013) of different cells have been established These are usually label-free methods depending on the physical properties, and high-throughput cell isolation can be achieved. In 2007, Nagrath et al developed a “CTC-chip” by using anti-EpCAM antibody–coated microposts in a microfluidic chip (Nagrath et al, 2007) This immunoaffinity platform achieved efficient and selective separation of viable CTCs from the peripheral blood samples, with an identified yield of CTCs reaching 99%, and achieved an approximately 50% purity. At the end of the review, we discuss some challenges of these nanomaterial-based immunocapture platforms that remain in clinical transformation
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