Skip to main content
Log in

Peptide NGR Modified TiO2 Nanofiber Substrate for Circulating Tumor Cells Capture

  • Research Article
  • Published:
Advanced Fiber Materials Aims and scope Submit manuscript

Abstract

The analysis of circulating tumor cells (CTCs) allows a noninvasive method of “real-time liquid biopsy” from the blood samples of cancer patients for the diagnosis of early-stage cancer, prognosis, and monitoring therapeutic response. In this study, we develop a simple, inexpensive, and reliable method that utilizes a small molecule peptide, the asparagine-glycine-arginine (NGR), as a capture probe for the selective enrichment and isolation of circulating tumor cells (CTCs). The multiscale TiO2 nanofibers are obtained by electrospinning and calcination. Bovine serum albumin (BSA) is decorated onto TiO2 nanofiber surfaces to inhibit non-target cell adhesion, while NGR peptides are conjugated onto the TiO2-BSA surface through the glutaraldehyde (GA) to specifically capture the target cells. The TiO2-BSA-NGR substrate exhibits a high capture sensitivity and efficiency from the mimical blood samples with PC-3 cancer cells as low as 10 cells/mL. The TiO2 nanofiber substrate can be a promising strategy for the capture and enumeration of CTCs in cancer progression monitoring.

Graphic Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Shen Z, Wu A, Chen X. Current detection technologies for circulating tumor cells.Chem Soc Rev. 2017;46:2038.

    Article  CAS  Google Scholar 

  2. Wang Z, Sun N, Liu M, Cao Y, Wang K, Wang J, Pei R. Multifunctional nanofibers for specific purification and release of CTCs. ACS Sens. 2017;2:547.

    Article  CAS  Google Scholar 

  3. Fan X, Jia C, Yang J, Li G, Mao H, Jin Q, Zhao J. A microfluidic chip integrated with a high-density PDMS-based microfiltration membrane for rapid isolation and detection of circulating tumor cells. Biosens Bioelectron. 2015;71:380.

    Article  CAS  Google Scholar 

  4. Gao W, Zhang X, Yuan H, Wang Y, Zhou H, Jin H, Jia C, Jin Q, Cong H, Zhao J. EGFR point mutation detection of single circulating tumor cells for lung cancer using a micro-well arrayBiosens Bioelectron. 2019;139:111326.

    Article  CAS  Google Scholar 

  5. Lecharpentier A, Vielh P, Perez-Moreno P, Planchard D, Soria JC, Farace F. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br J Cancer. 2011;105:1338.

    Article  CAS  Google Scholar 

  6. Zhao Y, Xu D, Tan W. Aptamer-functionalized nano/micro-materials for clinical diagnosis: isolation, release and bioanalysis of circulating tumor cells. Integr Biol. 2017;9:188.

    Article  Google Scholar 

  7. Sun N, Li X, Wang Z, Li Y, Pei R. High-purity capture of CTCs based on micro-beads enhanced isolation by size of epithelial tumor cells (ISET) method. Biosens Bioelectron. 2018;1022:157.

    Article  CAS  Google Scholar 

  8. Hu B, Rochefort H, Goldkorn A. Circulating tumor cells in prostate cancer. Cancers. 2013;5:1676.

    Article  Google Scholar 

  9. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329.

    Article  CAS  Google Scholar 

  10. Wang S, Wang H, Jiao J, Chen KJ, Owens GE, Kamei K, Sun J, Sherman DJ, Behrenbruch CP, Wu H, Tseng HR. Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew Chem Int Ed. 2009;48:8970.

    Article  CAS  Google Scholar 

  11. Sun N, Li X, Wang Z, Zhang R, Wang J, Wang K, Pei R. A multiscale TiO2 nanorod array for ultrasensitive capture of circulating tumor cells. ACS Appl Mater Interfaces. 2016;8:12638.

    Article  CAS  Google Scholar 

  12. Sun N, Liu M, Wang J, Wang Z, Li X, Jiang B, Pei R. Chitosan nanofibers for specific capture and nondestructive release of CTCs assisted by pCBMA brushes. Small. 2016;12:5090.

    Article  CAS  Google Scholar 

  13. Liu H, Wang Z, Chen C, Ding P, Sun N, Pei R. Dual-antibody modified PLGA nanofibers for specific capture of epithelial and mesenchymal CTCs. Colloids Surf B Biointerfaces. 20199;181:143.

    Article  CAS  Google Scholar 

  14. Sun N, Wang J, Ji L, Hong S, Dong J, Guo Y, Zhang K, Pei R. A cellular compatible chitosan nanoparticle surface for isolation and in situ culture of rare number CTCs. Small. 2015;11:5444.

    Article  CAS  Google Scholar 

  15. Chen C, Wang Z, Zhao Y, Cao Y, Ding P, Liu H, Su N, Pei R. A folic acid modified polystyrene nanosphere surface for circulating tumor cell capture. Anal Methods. 2019;11:5718.

    Article  CAS  Google Scholar 

  16. Zhang N, Deng Y, Tai Q, Cheng B, Zhao L, Shen Q, He R, Hong L, Liu W, Guo S, Liu K, Tseng HR, Xiong B, Zhao XZ. Electrospun TiO2 nanofiber-based cell capture assay for detecting circulating tumor cells from colorectal and gastric cancer patients. Adv Mater. 2012;24:2756.

    Article  CAS  Google Scholar 

  17. Gorges TM, Tinhofer I, Drosch M, Rose L, Zollner TM, Krahn T, von Ahsen O. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer. 2012;12:178.

    Article  CAS  Google Scholar 

  18. Wang Z, Sun N, Liu H, Chen C, Ding P, Yue X, Zou H, Xing C, Pei R. High-efficiency isolation and rapid identification of heterogeneous circulating tumor cells (CTCs) using dual-antibody-modified fluorescent-magnetic nanoparticles. ACS Appl Mater Interfaces. 20199;11:39586.

    Article  CAS  Google Scholar 

  19. Li F, Yang G, Aguilar ZP, Xiong Y, Xu H. Affordable and simple method for separating and detecting ovarian cancer circulating tumor cells using BSA coated magnetic nanoprobes modified with folic acid. Sens Actuators B Chem. 2018;262:611.

    Article  CAS  Google Scholar 

  20. Liu C, Xing J, Akakuru OU, Luo L, Sun S, Zou R, Yu Z, Fang Q, Wu A. Nanozymes-engineered metal-organic frameworks for catalytic cascades-enhanced synergistic cancer therapy. Nano Lett. 2019;19:5674.

    Article  CAS  Google Scholar 

  21. Shen Z, Song J, Zhou Z, Yung BC, Aronova MA, Li Y, Dai Y, Fan W, Liu Y, Li Z, Ruan H, Leapman RD, Lin L, Niu G, Chen X, Wu A. Dotted core-shell nanoparticles for T1-weighted MRI of tumors. Adv Mater. 2018;30:1803163.

    Article  Google Scholar 

  22. Wang X, Qiao X, Shang Y, Zhang S, Li Y, He H, Chen SZ. RGD and NGR modified TRAIL protein exhibited potent anti-metastasis effects on TRAIL-insensitive cancer cells in vitro and in vivo. Amino Acids. 20177;49:931.

    Article  CAS  Google Scholar 

  23. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998;279:377.

    Article  CAS  Google Scholar 

  24. Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F. Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer. BMC Cancer. 2008;8:74.

    Article  Google Scholar 

  25. Li ZJ, Cho CH. Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery. J Transl Med. 2012;10:S1.

    Article  Google Scholar 

  26. Zhu LP, Jiang JH, Zhu BK, Xu YY. Immobilization of bovine serum albumin onto porous polyethylene membranes using strongly attached polydopamine as a spacer. Colloids Surf B Biointerfaces. 2011;86:111.

    Article  CAS  Google Scholar 

  27. Dreyer DR, Miller DJ, Freeman BD, Paul DR, Bielawski CW. Perspectives on poly(dopamine). Chem Sci. 2013;4:3796.

    Article  CAS  Google Scholar 

  28. Pop-Georgievski O, Popelka S, Houska M, Chvostova D, Proks V, Rypacek F. Poly(ethylene oxide) layers grafted to dopamine-melanin anchoring layer: stability and resistance to protein adsorption. Biomacromol. 2011;12:3232.

    Article  CAS  Google Scholar 

  29. Ku SH, Ryu J, Hong SK, Lee H, Park CB. General functionalization route for cell adhesion on non-wetting surfaces. Biomaterials. 2010;31:2535.

    Article  CAS  Google Scholar 

  30. Jiang J, Zhu L, Zhu L, Zhu B, Xu Y. Surface characteristics of a self-polymerized dopamine coating deposited on hydrophobic polymer films. Langmuir. 2011;27:14180.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (21904135, 21575154, 21775160), the Natural Science Foundation of Jiangsu Province (BK20180250), the Science Foundation of Jiangxi Province (20192ACB21033), the CAS International Cooperation Key program (121E32KYSB20170025), the Jiangsu Province Six Talent Peaks program and the CAS/SAFEA International Innovation Teams program.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zhili Wang or Renjun Pei.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, C., Wu, Z., Ding, P. et al. Peptide NGR Modified TiO2 Nanofiber Substrate for Circulating Tumor Cells Capture. Adv. Fiber Mater. 2, 186–193 (2020). https://doi.org/10.1007/s42765-020-00040-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42765-020-00040-0

Keywords

Navigation