Multimodal CTC detection using stem cell antigen-specific immunosilica particles and immunofluorescent quantum dots
Source abstract
Abstract
Abstract Amid the COVID-19 pandemic, cancer continues to be the most devastating disease worldwide. Liquid biopsy of circulating tumor cells (CTCs) has recently become a painless and noninvasive tool for obtaining carcinoma cell samples for molecular profiling. Here, we report efficient detection and collection of cancer cells in blood samples by combining stem cell antigen (CD44)-specific immunosilica particles and immunofluorescent quantum dots with spectrally and temporally resolved single-photon counting. We accurately detect 1–10 cells among 100 cancer cells of the breast, lungs, or cervix in 1 mL blood samples. In addition, the bright and narrowband emission of CdSe/ZnS quantum dots enables temporally and spectrally resolved photon counting for multiplexed cancer cell detection. The cancer cell-specific and large immunosilica particles helped us collect the specific cells. We validate the detection efficiency and multimodality of this strategy by time-stamped and energy-dispersed single-photon counting of orange- and red-emitting quantum dots and green-fluorescing nuclei stained with Syto-13/25 dye. Thus, the present work highlights the prospects of multimodal CTC detection for noninvasive cancer screening and postsurgical or therapeutic follow-up.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Cancer Cells and Metastasis · Single-cell and spatial transcriptomics · Cancer Genomics and Diagnostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (46)
Show source-provided references
1. Delorey, T. M. et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature 595, 107–113 (2021).10.1038/s41586-021-03570-8 ↗
2. Bastard, P. et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370, eabd4585 (2021).10.1126/science.abd4585 ↗
3. Kumar, P., Sobhanan, J., Takano, Y. & Biju, V. Molecular recognition in the infection, replication, and transmission of COVID-19-causing SARS-CoV-2: an emerging interface of infectious disease, biological chemistry, and nanoscience. Npg. Asia Mater. 13, 14 (2021).10.1038/s41427-020-00275-8 ↗
4. Keller, L. & Pantel, K. Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells. Nat. Rev. Cancer 19, 553–567 (2019).10.1038/s41568-019-0180-2 ↗
5. Xu, C. & Pu, K. Second near-infrared photothermal materials for combinational nanotheranostics. Chem. Soc. Rev. 50, 1111–1137 (2021).10.1039/D0CS00664E ↗
6. Shen, Z. et al. Strategies to improve photodynamic therapy efficacy by relieving the tumor hypoxia environment. NPG Asia Mater. 13, 39 (2021).10.1038/s41427-021-00303-1 ↗
7. Laxman, K. et al., Bioinspired carrier-free peptide conjugated BF2-oxasmaragdyrin dye-based nano self-assemblies: a photostable NIR cancer theragnostic agent. NPG Asia Mater. 12, 75 https://doi.org/10.1038/s41427-020-00256-x (2020).10.1038/s41427-020-00256-x ↗
8. Hodgkinson, C. L. et al. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat. Med. 20, 897–903 (2014).10.1038/nm.3600 ↗
9. Alix-Panabieres, C. & Pantel, K. Challenges in circulating tumour cell research. Nat. Rev. Cancer 14, 623–631 (2014).10.1038/nrc3820 ↗
10. Shen, Z., Wu, A. & Chen, X. Current detection technologies for circulating tumor cells. Chem. Soc. Rev. 46, 2038–2056 (2017).10.1039/C6CS00803H ↗
11. Li, W. et al. Emerging nanotechnologies for liquid biopsy: the detection of circulating tumor cells and extracellular vesicles. Adv. Mater. 31, 1805344 (2019).10.1002/adma.201805344 ↗
12. Baccelli, I. et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat. Biotechnol. 31, 539–544 (2013).10.1038/nbt.2576 ↗
13. Ashworth, T. R. A Case of Cancer in Which Cells Similar to Those in the Tumours Were Seen in the Blood after Death. T. R. Med. J. Aust. 14, 146 (1869).
14. Kim, M. Y. et al. Tumor self-seeding by circulating cancer cells. Cell 139, 1315–26 (2009).10.1016/j.cell.2009.11.025 ↗
15. Ring, A., Smith, I. E. & Dowsett, M. Circulating tumour cells in breast cancer. Lancet Oncol. 5, 79–88 (2004).10.1016/S1470-2045(04)01381-6 ↗
16. Cabel, L. et al. Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial. Br. J. Cancer 124, 1207–1213 (2021).10.1038/s41416-020-01227-3 ↗
17. Bidard, F. C. et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 15, 406–414 (2014).10.1016/S1470-2045(14)70069-5 ↗
18. de bono, J. S. et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res. 14, 6302–6309 (2008).10.1158/1078-0432.CCR-08-0872 ↗
19. Khoo, B. L. et al. Liquid biopsy and therapeutic response: circulating tumor cell cultures for evaluation of anticancer treatment. Sci. Adv. 2, e1600274 (2016).10.1126/sciadv.1600274 ↗
20. Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).10.1038/nature06385 ↗
21. Cristofanilli, M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med 351, 781–791 (2004).10.1056/NEJMoa040766 ↗
22. Wu, L. L. et al. Spectrally combined encoding for profiling heterogeneous circulating tumor cells using a multifunctional nanosphere‐mediated microfluidic platform. Angew. Chem. Int. Ed. 59, 11240–11244 (2020).10.1002/anie.201914468 ↗
23. Schiro, P. G. et al. Sensitive and high-throughput isolation of rare cells from peripheral blood with ensemble-decision aliquot ranking. Angew. Chem. Int. Ed. 51, 4618–4622 (2012).10.1002/anie.201108695 ↗
24. Yoon, H. J. et al. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat. Nanotechnol. 8, 735–741 (2013).10.1038/nnano.2013.194 ↗
25. Wang, S. et al. Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew. Chem. Int. Ed. 50, 3084–3088 (2011).10.1002/anie.201005853 ↗
26. Park, M. H. et al. Enhanced isolation and release of circulating tumor cells using nanoparticle binding and ligand exchange in a microfluidic chip. J. Am. Chem. Soc. 139, 2741–2749 (2017).10.1021/jacs.6b12236 ↗
27. Poudineh, M. et al. Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nat. Nanotechnol. 12, 274–281 (2017).10.1038/nnano.2016.239 ↗
28. Lu, N. N. et al. Biotin-triggered decomposable immunomagnetic beads for capture and release of circulating tumor cells. ACS Appl. Mater. Interfaces 7, 8817–8826 (2015).10.1021/acsami.5b01397 ↗
29. Rosenholm, J. M. et al. Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano 3, 197–206 (2009).10.1021/nn800781r ↗
30. Wang, L., Asghar, W., Demirci, U. & Wan, Y. Nanostructured substrates for isolation of circulating tumor cells. Nano Today 8, 374–387 (2013).10.1016/j.nantod.2013.07.001 ↗
31. Yoo, C. E. et al. Highly dense, optically inactive silica microbeads for the isolation and identification of circulating tumor cells. Biomaterials 75, 271–278 (2016).10.1016/j.biomaterials.2015.10.033 ↗
32. Biju, V., Itoh, T. & Ishikawa, M. Delivering quantum dots to cells: bioconjugated quantum dots for targeted and nonspecific extracellular and intracellular imaging. Chem. Soc. Rev. 39, 3031–3056 (2010).10.1039/b926512k ↗
33. Biju, V. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem. Soc. Rev. 43, 744–764 (2014).10.1039/C3CS60273G ↗
34. Anas, A. et al. Clathrin-mediated endocytosis of quantum dot-peptide conjugates in living cells. ACS nano 3, 2419–2429 (2009).10.1021/nn900663r ↗
35. Shibu, E. S. et al. Photouncaging nanoparticles for MRI and fluorescence imaging in vitro and in vivo. ACS Nano 7, 9851–9859 (2013).10.1021/nn4043699 ↗
36. Payne, R. E. et al. Measurements of EGFR expression on circulating tumor cells are reproducible over time in metastatic breast cancer patients. Pharmacogenomics 10, 51–57 (2009).10.2217/14622416.10.1.51 ↗
37. Flores, L. M. et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br. J. Cancer 102, 1495–502 (2010).10.1038/sj.bjc.6605676 ↗
38. Lecharpentier, A. et al. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br. J. Cancer 105, 1338–1341 (2011).10.1038/bjc.2011.405 ↗
39. Yu, M. et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339, 580–584 (2013).10.1126/science.1228522 ↗
40. Mohamadi, R. M. et al. Nanoparticle‐mediated binning and profiling of heterogeneous circulating tumor cell subpopulations. Angew. Chem. Int. Ed. 54, 139–143 (2015).10.1002/anie.201409376 ↗
41. Grillet, F. et al. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut 66, 1802–1810 (2017).10.1136/gutjnl-2016-311447 ↗
42. Chen, C., Zhao, S., Karnad, A. & Freeman, J. W. Anti-GD2/4-1BB chimeric antigen receptor T cell therapy for the treatment of Chinese melanoma patients. J. Hematol. Oncol. 11, 1 (2018).10.1186/s13045-017-0548-2 ↗
43. Poortmans, P. M. et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N. Engl. J. Med. 373, 317–327 (2015).10.1056/NEJMoa1415369 ↗
44. Cheng, B. et al. Quantification of rare cancer cells in patients with gastrointestinal cancer by nanostructured substrate. Transl. Oncol. 7, 720–725 (2014).10.1016/j.tranon.2014.10.001 ↗
45. Shibu, E. S. et al. Singlet-oxygen-sensitizing near-infrared-fluorescent multimodal nanoparticles. Angew. Chem. Int. Ed. 52, 10559–10563 (2013).10.1002/anie.201304264 ↗
46. Kawashima, N. et al. Reversible dimerization of EGFR revealed by single-molecule fluorescence imaging using quantum dots. Chem. Eur. J. 16, 1186–1192 (2010).10.1002/chem.200902963 ↗