Advertisement

Journal of Materials Science

, Volume 52, Issue 12, pp 6907–6916 | Cite as

Silica nanostructured platform for affinity capture of tumor-derived exosomes

  • Parissa Ziaei
  • Jonathan J. Geruntho
  • Oscar G. Marin-Flores
  • Clifford E. Berkman
  • M. Grant NortonEmail author
Original Paper

Abstract

Early diagnosis of prostate cancer and evaluation of appropriate treatment options requires development of effective and high-throughput selective capture technology for exosomes that are positive for the expression of enzyme-biomarker, prostate-specific membrane antigen (PSMA). Exosomes are small secreted vesicles that play a key role in intercellular communication and cancer progression. PSMA is highly enriched in exosomes excreted by PSMA+ prostate cancer cells. Using PSMA+ cells from the well-established prostate cancer cell line (LNCaP), the secreted exosomes were collected and isolated from the culture medium. The tumor-derived exosomes were selectively captured using a novel silica nanostructure support that had been functionalized with the small-molecule ligand TG97, a known inhibitor of PSMA enzymatic activity that binds irreversibly in the active site of PSMA. The concept was demonstrated using a single cancer type (i.e., prostate cancer), but based on the data obtained the approach may be applicable to a broad panel of biomarker ligands for selective capture of biomarker-positive exosomes from an array of cell types. The approach demonstrated herein overcomes many of the limitations of alternative methods that are often ineffective in isolating tumor-derived exosomes from those derived from normal tissue because of the low yield recovery and the time required for the process. A further advantage is the ability to isolate a specific subpopulation of exosomes relying on the expression of a specific surface marker as well as improved exosome recovery rate.

Keywords

Contact Angle LNCaP Cell Complete Growth Medium Affinity Capture Specific Surface Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program under Award No. W81XWH-14-1-0449. The authors are grateful for technical assistance from Dr. Christine Davitt and Dr. Valerie Lynch-Holm at the Franceschi Microscopy and Imaging Center and Dr. Amit Bandyopadhyay and Yanning Zhang for assistance with the contact angle study.

Supplementary material

10853_2017_905_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 kb)

References

  1. 1.
    Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis and drug resistance: a comprehensive review. Cancer Metastasis Rev. doi: 10.1007/s10555-013-9441-9 Google Scholar
  2. 2.
    Van Niel G et al (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121(2):337–349CrossRefGoogle Scholar
  3. 3.
    Logozzi M et al (2009) High levels of exosomes expressing CD63 and Caveolin-1 in plasma of melanoma patients. PLoS ONE 4(4):e5219CrossRefGoogle Scholar
  4. 4.
    Pisitkun T, Shen R-F, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 101(36):13368–13373CrossRefGoogle Scholar
  5. 5.
    Michael A et al (2010) Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 16(1):34–38CrossRefGoogle Scholar
  6. 6.
    Keller S et al (2007) CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int 72(9):1095–1102CrossRefGoogle Scholar
  7. 7.
    Andre F et al (2002) Malignant effusions and immunogenic tumour-derived exosomes. The Lancet 360(9329):295–305CrossRefGoogle Scholar
  8. 8.
    Xiao D et al (2012) Identifying mRNA, MicroRNA and protein profiles of melanoma exosomes. PLoS ONE 7(10):e46874CrossRefGoogle Scholar
  9. 9.
    Sceneay J, Smyth M, Möller A (2013) The pre-metastatic niche: finding common ground. Cancer Metastasis Rev 32(3–4):449–464CrossRefGoogle Scholar
  10. 10.
    Liu T, Mendes DE, Berkman CE (2014) Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells. Int J Oncol 44(3):918–922Google Scholar
  11. 11.
    Momen-Heravi F et al (2013) Current methods for the isolation of extracellular vesicles. Biol Chem 394:1253Google Scholar
  12. 12.
    Kanwar SS et al (2014) Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip 14(11):1891–1900CrossRefGoogle Scholar
  13. 13.
    Chen C et al (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10(4):505–511CrossRefGoogle Scholar
  14. 14.
    Wang Z et al (2013) Ciliated micropillars for the microfluidic-based isolation of nanoscale lipid vesicles. Lab Chip 13(15):2879–2882CrossRefGoogle Scholar
  15. 15.
    Davies RT et al (2012) Microfluidic filtration system to isolate extracellular vesicles from blood. Lab Chip 12(24):5202–5210CrossRefGoogle Scholar
  16. 16.
    Im H et al (2014) Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 32(5):490–495CrossRefGoogle Scholar
  17. 17.
    Liga A et al (2015) Exosome isolation: a microfluidic road-map. Lab Chip 15(11):2388–2394CrossRefGoogle Scholar
  18. 18.
    Ko J, Carpenter E, Issadore D (2016) Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro-/nano-based devices. Analyst 141(2):450–460CrossRefGoogle Scholar
  19. 19.
    Fu H et al (2012) Threonine aldolase immobilization on different supports for engineering of productive, cost-efficient enzymatic microreactors. Chem Eng J 207–208:564–576CrossRefGoogle Scholar
  20. 20.
    Pondman KM et al (2015) Magnetic drug delivery with FePd nanowires. J Magn Magn Mater 380:299–306CrossRefGoogle Scholar
  21. 21.
    Lee J-H et al (2016) Spontaneous internalization of cell penetrating peptide-modified nanowires into primary neurons. Nano Lett 16(2):1509–1513CrossRefGoogle Scholar
  22. 22.
    Schilke KF et al (2010) A novel enzymatic microreactor with Aspergillus oryzae β-galactosidase immobilized on silicon dioxide nanosprings. Biotechnol Prog 26(6):1597–1605CrossRefGoogle Scholar
  23. 23.
    McIlroy DN et al (2004) Nanospring formation—unexpected catalyst mediated growth. J Phys Condens Matter 16(12):R415CrossRefGoogle Scholar
  24. 24.
    McIlroy DN et al (2001) Nanosprings. Appl Phys Lett 79(10):1540–1542CrossRefGoogle Scholar
  25. 25.
    Lidong W et al (2006) High yield synthesis and lithography of silica-based nanospring mats. Nanotechnology 17(11):S298CrossRefGoogle Scholar
  26. 26.
    Ganguly T et al (2015) A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer. Nuclear Med Biol 42(10):780–787CrossRefGoogle Scholar
  27. 27.
    Tremblay M-È, Riad M, Majewska AK (2010) Preparation of mouse brain tissue for immunoelectron microscopy. J Vis Exp JoVE 41:2021Google Scholar
  28. 28.
    Yang Z et al (2008) Streptavidin-functionalized three-dimensional ordered nanoporous silica film for highly efficient chemiluminescent immunosensing. Adv Funct Mater 18(24):3991–3998CrossRefGoogle Scholar
  29. 29.
    Zhao J et al (2015) Super-hydrophobic surfaces of SiO2-coated SiC nanowires: fabrication, mechanism and ultraviolet-durable super-hydrophobicity. J Colloid Interface Sci 444:33–37CrossRefGoogle Scholar
  30. 30.
    Cassie ABD, Baxter S (1944) Wettability of porous surfaces. Trans Faraday Soc 40:546–551CrossRefGoogle Scholar
  31. 31.
    Daoud WA, Xin JH, Tao X (2004) Superhydrophobic silica nanocomposite coating by a low-temperature process. J Am Ceram Soc 87(9):1782–1784CrossRefGoogle Scholar
  32. 32.
    Daoud WA, Xin JH, Tao X (2006) Synthesis and characterization of hydrophobic silica nanocomposites. Appl Surf Sci 252(15):5368–5371CrossRefGoogle Scholar
  33. 33.
    Slack JK et al (2001) Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene 20(10):1152–1163CrossRefGoogle Scholar
  34. 34.
    Zomer A et al (2010) Exosomes: fit to deliver small RNA. Commun Integr Biol 3(5):447–450CrossRefGoogle Scholar
  35. 35.
    Conde-Vancells J et al (2008) Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 7(12):5157–5166CrossRefGoogle Scholar
  36. 36.
    Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383CrossRefGoogle Scholar
  37. 37.
    Raposo G et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Materials Science and Engineering ProgramWashington State UniversityPullmanUSA
  2. 2.Department of ChemistryWashington State UniversityPullmanUSA
  3. 3.School of Mechanical and Materials EngineeringWashington State UniversityPullmanUSA
  4. 4.Voiland School of Chemical Engineering and BioengineeringWashington State UniversityPullmanUSA

Personalised recommendations