pp 1-21 | Cite as

Targeting Glioma Cancer Cells with Fluorescent Nanodiamonds via Integrin Receptors

  • Jitka Neburkova
  • Miroslav Hajek
  • Ivan Rehor
  • Jiri Schimer
  • Frantisek Sedlak
  • Jan Stursa
  • Martin Hruby
  • Petr Cigler
Protocol
Part of the Methods in Pharmacology and Toxicology book series

Abstract

Glioblastomas, aggressive and highly vascularized brain tumors, overexpress αvβ3 integrins, which are widely exploited for cancer diagnostics and therapy. Proteins and peptides containing the RGD sequence bind αvβ3 integrins. Here, we describe detailed protocols for preparation and testing of fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell. When the surface of these particles was modified with a cyclic RGD peptide, they selectively targeted integrin αvβ3 receptors on U-87 MG glioblastoma cells with high internalization efficacy. The modified particles enabled background-free near-infrared imaging of cells, showed excellent colloidal stability in culture media, and exhibited negligible cytotoxicity.

Keywords

Background-free imaging Fluorescent nanodiamond Glioma RGD peptide Targeting αvβ3 integrin 

Notes

Acknowledgments

This work was supported by the Czech Science Foundation project Nr. 16-16336S (to J.N. and P.C.) and Nr. 16-03156S (to M.H.). Irradiations were performed at the CANAM infrastructure of the NPI CAS Rez supported through MŠMT project No. LM2011019. Imaging was performed on confocal microscope supported by Project NPU I, LO 1302 from the Ministry of Education, Youth and Sports of the Czech Republic.

References

  1. 1.
    Resch-Genger U, Grabolle M, Cavaliere-Jaricot S et al (2008) Quantum dots versus organic dyes as fluorescent labels. Nat Methods 5:763–775CrossRefPubMedGoogle Scholar
  2. 2.
    Bardhan R, Lal S, Joshi A, Halas NJ (2011) Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc Chem Res 44:936–946CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Das M, Mohanty C, Sahoo SK (2009) Ligand-based targeted therapy for cancer tissue. Expert Opin Drug Deliv 6:285–304CrossRefPubMedGoogle Scholar
  4. 4.
    Delehanty JB, Boeneman K, Bradburne CE et al (2010) Peptides for specific intracellular delivery and targeting of nanoparticles: implications for developing nanoparticle-mediated drug delivery. Ther Deliv 1:411–433CrossRefPubMedGoogle Scholar
  5. 5.
    Hersel U, Dahmen C, Kessler H (2003) RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 24:4385–4415CrossRefPubMedGoogle Scholar
  6. 6.
    Liu S (2006) Radiolabeled multimeric cyclic RGD peptides as integrin αv β3 targeted radiotracers for tumor imaging. Mol Pharm 3:472–487CrossRefPubMedGoogle Scholar
  7. 7.
    Ruoslahti E (2012) Peptides as targeting elements and tissue penetration devices for nanoparticles. Adv Mater 24:3747–3756CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schottelius M, Wester H-J (2009) Molecular imaging targeting peptide receptors. Methods 48:161–177CrossRefPubMedGoogle Scholar
  9. 9.
    Danhier F, Breton AL, Préat V (2012) RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Mol Pharm 9:2961–2973CrossRefPubMedGoogle Scholar
  10. 10.
    Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25CrossRefPubMedGoogle Scholar
  11. 11.
    Liu S (2009) Radiolabeled cyclic RGD peptides as integrin αvβ3-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem 20:2199–2213CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ruoslahti E (1996) RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 12:697–715CrossRefPubMedGoogle Scholar
  13. 13.
    Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RGD and integrins. Science 238:491–497ADSCrossRefPubMedGoogle Scholar
  14. 14.
    Ruoslahti E, Bhatia SN, Sailor MJ (2010) Targeting of drugs and nanoparticles to tumors. J Cell Biol 188:759–768CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Liu Z, Wang F, Chen X (2008) Integrin αvβ3-targeted cancer therapy. Drug Dev Res 69:329–339CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Temming K, Schiffelers RM, Molema G, Kok RJ (2005) RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Updat 8:381–402CrossRefPubMedGoogle Scholar
  17. 17.
    Kozák O, Sudolská M, Pramanik G et al (2016) Photoluminescent carbon nanostructures. Chem Mater 28:4085–4128CrossRefGoogle Scholar
  18. 18.
    Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9:123–128CrossRefPubMedGoogle Scholar
  19. 19.
    Gruber A, Dräbenstedt A, Tietz C et al (1997) Scanning confocal optical microscopy and magnetic resonance on single defect centers. Science 276:2012–2014CrossRefGoogle Scholar
  20. 20.
    Tisler J, Reuter R, Lämmle A et al (2011) Highly efficient FRET from a single nitrogen-vacancy center in nanodiamonds to a single organic molecule. ACS Nano 5:7893–7898CrossRefPubMedGoogle Scholar
  21. 21.
    Shi X, Tu Y, Liu X et al (2013) Photobleaching of quantum dots by non-resonant light. Phys Chem Chem Phys 15:3130–3132CrossRefPubMedGoogle Scholar
  22. 22.
    Parak WJ, Pellegrino T, Plank C (2005) Labelling of cells with quantum dots. Nanotechnology 16:R9–R25ADSCrossRefPubMedGoogle Scholar
  23. 23.
    Balasubramanian G, Chan IY, Kolesov R et al (2008) Nanoscale imaging magnetometry with diamond spins under ambient conditions. Nature 455:648–651ADSCrossRefPubMedGoogle Scholar
  24. 24.
    Maze JR, Stanwix PL, Hodges JS et al (2008) Nanoscale magnetic sensing with an individual electronic spin in diamond. Nature 455:644–647ADSCrossRefPubMedGoogle Scholar
  25. 25.
    Laraoui A, Hodges JS, Meriles CA (2012) Nitrogen-vacancy-assisted magnetometry of paramagnetic centers in an individual diamond nanocrystal. Nano Lett 12:3477–3482ADSCrossRefPubMedGoogle Scholar
  26. 26.
    Dolde F, Fedder H, Doherty MW et al (2011) Electric-field sensing using single diamond spins. Nat Phys 7:459–463CrossRefGoogle Scholar
  27. 27.
    Petrakova V, Rehor I, Stursa J et al (2015) Charge-sensitive fluorescent nanosensors created from nanodiamonds. Nanoscale 7:12307–12311ADSCrossRefPubMedGoogle Scholar
  28. 28.
    Petrakova V, Benson V, Buncek M et al (2016) Imaging of transfection and intracellular release of intact, non-labeled DNA using fluorescent nanodiamonds. Nanoscale 8:12002–12012ADSCrossRefPubMedGoogle Scholar
  29. 29.
    Havlik J, Raabova H, Gulka M et al (2016) Benchtop fluorination of fluorescent nanodiamonds on a preparative scale: toward unusually hydrophilic bright particles. Adv Funct Mater 26(23):4134–4142. doi:10.1002/adfm.201504857 CrossRefGoogle Scholar
  30. 30.
    Petrakova V, Nesladek M, Taylor A et al (2011) Luminescence properties of engineered nitrogen vacancy centers in a close surface proximity. Phys Status Solidi A 208:2051–2056ADSCrossRefGoogle Scholar
  31. 31.
    Rendler T, Neburkova J, Zemek O et al (2017) Optical imaging of localized chemical events using programmable diamond quantum nanosensors. Nat Commun 8:14701ADSCrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Wu T-J, Tzeng Y-K, Chang W-W et al (2013) Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds. Nat Nanotechnol 8:682–689ADSCrossRefPubMedGoogle Scholar
  33. 33.
    Mohan N, Chen C-S, Hsieh H-H et al (2010) In vivo imaging and toxicity assessments of fluorescent nanodiamonds in Caenorhabditis elegans. Nano Lett 10:3692–3699ADSCrossRefPubMedGoogle Scholar
  34. 34.
    Slegerova J, Hajek M, Rehor I et al (2015) Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells. Nanoscale 7:415–420ADSCrossRefPubMedGoogle Scholar
  35. 35.
    Chow EK, Zhang X-Q, Chen M et al (2011) Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci Transl Med 3:73ra21CrossRefPubMedGoogle Scholar
  36. 36.
    Alhaddad A, Adam M-P, Botsoa J et al (2011) Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells. Small 7:3087–3095CrossRefPubMedGoogle Scholar
  37. 37.
    Zhao L, Xu Y-H, Qin H et al (2014) Platinum on nanodiamond: a promising prodrug conjugated with stealth polyglycerol, targeting peptide and acid-responsive antitumor drug. Adv Funct Mater 24:5348–5357CrossRefGoogle Scholar
  38. 38.
    Rehor I, Lee KL, Chen K et al (2015) Plasmonic nanodiamonds: targeted core–shell type nanoparticles for cancer cell thermoablation. Adv Healthc Mater 4:460–468CrossRefPubMedGoogle Scholar
  39. 39.
    Rehor I, Slegerova J, Havlik J et al (2016) Nanodiamonds: behavior in biological systems and emerging bioapplications. In: Zhang M, Naik RR, Dai L (eds) Carbon nanomaterial biomedical application. Springer International Publishing, Cham, pp 319–361CrossRefGoogle Scholar
  40. 40.
    Slegerova J, Rehor I, Havlik J et al (2014) Nanodiamonds as intracellular probes for imaging in biology and medicine. In: Prokop A, Iwasaki Y, Harada A (eds) Intracellular delivery II. Springer, Dordrecht, pp 363–401CrossRefGoogle Scholar
  41. 41.
    Weng M-F, Chiang S-Y, Wang N-S, Niu H (2009) Fluorescent nanodiamonds for specifically targeted bioimaging: application to the interaction of transferrin with transferrin receptor. Diam Relat Mater 18:587–591ADSCrossRefGoogle Scholar
  42. 42.
    Zhang B, Li Y, Fang C-Y et al (2009) Receptor-mediated cellular uptake of folate-conjugated fluorescent nanodiamonds: a combined ensemble and single-particle study. Small 5:2716–2721CrossRefPubMedGoogle Scholar
  43. 43.
    Dahoumane SA, Nguyen MN, Thorel A et al (2009) Protein-functionalized hairy diamond nanoparticles. Langmuir 25:9633–9638CrossRefPubMedGoogle Scholar
  44. 44.
    Rehor I, Slegerova J, Kucka J et al (2014) Fluorescent nanodiamonds embedded in biocompatible translucent shells. Small 10:1106–1115CrossRefPubMedGoogle Scholar
  45. 45.
    Neburkova J, Vavra J, Cigler P (2017) Coating nanodiamonds with biocompatible shells for applications in biology and medicine. Curr Opin Solid State Mater Sci 21(1):43–53ADSCrossRefGoogle Scholar
  46. 46.
    Boudou J-P, David M-O, Joshi V et al (2013) Hyperbranched polyglycerol modified fluorescent nanodiamond for biomedical research. Diam Relat Mater 38:131–138ADSCrossRefGoogle Scholar
  47. 47.
    Zhao L, Takimoto T, Ito M et al (2011) Chromatographic separation of highly soluble diamond nanoparticles prepared by polyglycerol grafting. Angew Chem Int Ed 50:1388–1392CrossRefGoogle Scholar
  48. 48.
    Rehor I, Mackova H, Filippov SK et al (2014) Fluorescent nanodiamonds with bioorthogonally reactive protein-resistant polymeric coatings. Chem Plus Chem 79:21–24Google Scholar
  49. 49.
    Takimoto T, Chano T, Shimizu S et al (2010) Preparation of fluorescent diamond nanoparticles stably dispersed under a physiological environment through multistep organic transformations. Chem Mater 22:3462–3471CrossRefGoogle Scholar
  50. 50.
    Lee JW, Lee S, Jang S et al (2013) Preparation of non-aggregated fluorescent nanodiamonds (FNDs) by non-covalent coating with a block copolymer and proteins for enhancement of intracellular uptake. Mol BioSyst 9:1004–1011CrossRefPubMedGoogle Scholar
  51. 51.
    Man HB, Lam R, Chen M et al (2012) Nanodiamond-therapeutic complexes embedded within poly(ethylene glycol) diacrylate hydrogels mediating sequential drug elution. Phys Status Solidi A 209:1811–1818ADSCrossRefGoogle Scholar
  52. 52.
    Marcon L, Kherrouche Z, Lyskawa J et al (2011) Preparation and characterization of Zonyl-coated nanodiamonds with antifouling properties. Chem Commun 47:5178–5180CrossRefGoogle Scholar
  53. 53.
    Kopecek J (2013) Polymer–drug conjugates: origins, progress to date and future directions. Adv Drug Deliv Rev 65:49–59CrossRefPubMedGoogle Scholar
  54. 54.
    Iinuma H, Maruyama K, Okinaga K et al (2002) Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer. Int J Cancer 99:130–137CrossRefPubMedGoogle Scholar
  55. 55.
    Hong V, Presolski SI, Ma C, Finn MG (2009) Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation. Angew Chem Int Ed 48:9879–9883CrossRefGoogle Scholar
  56. 56.
    Lallana E, Sousa-Herves A, Fernandez-Trillo F et al (2012) Click chemistry for drug delivery nanosystems. Pharm Res 29:1–34CrossRefPubMedGoogle Scholar
  57. 57.
    Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10:9–22CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Carboni B, Benalil A, Vaultier M (1993) Aliphatic amino azides as key building blocks for efficient polyamine syntheses. J Org Chem 58:3736–3741CrossRefGoogle Scholar
  59. 59.
    Havlik J, Petrakova V, Rehor I et al (2013) Boosting nanodiamond fluorescence: towards development of brighter probes. Nanoscale 5:3208–3211ADSCrossRefPubMedGoogle Scholar
  60. 60.
    Stursa J, Havlik J, Petrakova V et al (2016) Mass production of fluorescent nanodiamonds with a narrow emission intensity distribution. Carbon 96:812–818CrossRefGoogle Scholar
  61. 61.
    Rehor I, Cigler P (2014) Precise estimation of HPHT nanodiamond size distribution based on transmission electron microscopy image analysis. Diam Relat Mater 46:21–24ADSCrossRefGoogle Scholar

Copyright information

©  2017

Authors and Affiliations

  • Jitka Neburkova
    • 1
    • 2
  • Miroslav Hajek
    • 1
  • Ivan Rehor
    • 1
  • Jiri Schimer
    • 1
  • Frantisek Sedlak
    • 1
    • 2
    • 5
  • Jan Stursa
    • 3
  • Martin Hruby
    • 4
  • Petr Cigler
    • 1
  1. 1.Institute of Organic Chemistry and Biochemistry of the CASPrague 6Czech Republic
  2. 2.First Faculty of MedicineCharles UniversityPrague 2Czech Republic
  3. 3.Nuclear Physics Institute of the CAS250 68 Rez near PragueCzech Republic
  4. 4.Institute of Macromolecular Chemistry of the CASPrague 6Czech Republic
  5. 5.Department of Genetics and Microbiology, Faculty of ScienceCharles UniversityPrague 2Czech Republic

Personalised recommendations