Journal of Nanoparticle Research

, Volume 11, Issue 4, pp 775–783 | Cite as

Aptamer-modified gold nanoparticles for targeting breast cancer cells through light scattering

  • Yu-Fen Huang
  • Yang-Wei Lin
  • Zong-Hong Lin
  • Huan-Tsung Chang
Research Paper


In this study, we demonstrated the potential use of nucleic acid ligand (aptamers) conjugated gold nanoparticles (AuNPs) for cancer cell detection. Through specific binding of the aptamers toward platelet-derived growth factor (PDGF), MDA-MB-231 and Hs578T cells (cancer cells) that over-express PDGF, interact with Apt-AuNPs to a greater extent than do H184B5F5/M10 cells (normal cells). These results were confirmed through inductively coupled plasma mass spectrometry measurements of the gold ion concentrations within these cells. Aggregation of the Apt-AuNPs in the cytoplasm of the cancer cells led to the generation of an intense scattered light upon photo-illumination; this phenomenon allows the differentiation of cancer cells from normal cells using a dark field optical microscope. The presence of Apt-AuNPs suppressed the proliferation of MDA-MB-231 cancer cells, but not H184B5F5/M10 cells.


Aptamer Gold nanoparticles Breast cancer cells Imaging Proliferation Nanomedicine 


  1. Alivisatos AP, Gu W, Larabell C (2005) Quantum dots as cellular probes. Annu Rev Biomed Eng 7:55–76PubMedCrossRefGoogle Scholar
  2. Bhattacharya R et al (2004) Gold nanoparticles inhibit VEGF165-induced proliferation of HUVEC cells. Nano Lett 4(12):2479–2481CrossRefADSGoogle Scholar
  3. Bronzert DA et al (1987) Synthesis and secretion of platelet-derived growth-factor by human-breast cancer cell-lines. Proc Natl Acad Sci USA 84(16):5763–5767PubMedCrossRefADSGoogle Scholar
  4. Chan WCW, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281(5385):2016–2018PubMedCrossRefADSGoogle Scholar
  5. Chen J et al (2005) Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett 5(3):473–477PubMedCrossRefADSGoogle Scholar
  6. Coltrera MD, Wang J, Porter PL, Gown AM (1995) Expression of platelet-derived growth-factor B-chain and the platelet-derived growth-factor receptor-beta subunit in human breast-tissue and breast-carcinoma. Cancer Res 55(12):2703–2708PubMedGoogle Scholar
  7. Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1(3):325–327PubMedCrossRefGoogle Scholar
  8. de la Fuente JM, Berry CC, Riehle MO, Curtis ASG (2006) Nanoparticle targeting at cells. Langmuir 22(7):3286–3293CrossRefGoogle Scholar
  9. El-Sayed IH, Huang X, El-Sayed MA (2005) Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett 5(5):829–834PubMedCrossRefADSGoogle Scholar
  10. Farokhzad OC et al (2004) Nanopartide-aptamer bioconjugates: a new approach for targeting prostate cancer cells. Cancer Res 64(21):7668–7672PubMedCrossRefGoogle Scholar
  11. Farokhzad OC et al (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci USA 103(16):6315–6320PubMedCrossRefADSGoogle Scholar
  12. Floege J et al (1999) Novel approach to specific growth factor inhibition in vivo: antagonism of platelet-derived growth factor inGlomerulonephritis by aptamers. Am J Pathol 154(1):169–179PubMedGoogle Scholar
  13. Frens G (1973) Controlled nucleation for regulation of particle-size in monodisperse gold suspensions. Nat Phys Sci 241(105):20–22ADSGoogle Scholar
  14. Fukumori Y, Ichikawa H (2006) Nanoparticles for cancer therapy and diagnosis. Adv Powder Technol 17(1):1–28CrossRefGoogle Scholar
  15. Grabar KC, Freeman RG, Hommer MB, Natan MJ (1995) Preparation and characterization of Au colloid monolayers. Anal Chem 67(4):735–743CrossRefGoogle Scholar
  16. Green LS et al (1996) Inhibitory DNA ligands to platelet-derived growth factor B-chain. Biochemistry 35(45):14413–14424PubMedCrossRefGoogle Scholar
  17. Green R, Ellington AD, Szostak JW (1990) In vitro genetic-analysis of the tetrahymena self-splicing intron. Nature 347(6291):406–408PubMedCrossRefADSGoogle Scholar
  18. Hamula CLA, Guthrie JW, Zhang H, Li X-F, Le XC (2006) Selection and analytical applications of aptamers. Trac-Trends Anal Chem 25(7):681–691CrossRefGoogle Scholar
  19. Heldin C-H, Westermark B (1999) Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79(4):1283–1316PubMedGoogle Scholar
  20. Herr JK, Smith JE, Medley CD, Shangguan D, Tan W (2006) Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells. Anal Chem 78(9):2918–2924PubMedCrossRefGoogle Scholar
  21. Horisberger M (1981) Colloidal gold—a cytochemical marker for light and fluorescent microscopy and for transmission and scanning electron-microscopy. Scan Electron Micros II:9–32Google Scholar
  22. Hu M et al (2006) Gold nanostructures: engineering their plasmonic properties for biomedical applications. Chem Soc Rev 35(11):1084–1094PubMedCrossRefGoogle Scholar
  23. Huang C-C, Huang Y-F, Cao Z, Tan W, Chang H-T (2005) Aptamer-modified gold nanoparticles for colorimetric determination of platelet-derived growth factors and their receptors. Anal Chem 77(17):5735–5741PubMedCrossRefGoogle Scholar
  24. Huang X, El-Sayed IH, Qian W, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128(6):2115–2120PubMedCrossRefGoogle Scholar
  25. Jain KK (2005) Nanotechnology-based drug delivery for cancer. Technol Cancer Res Treat 4(4):407–416PubMedGoogle Scholar
  26. Jana NR, Gearheart L, Murphy CJ (2001) Seeding growth for size control of 5–40 nm diameter gold nanoparticles. Langmuir 17(22):6782–6786CrossRefGoogle Scholar
  27. Leitzel K et al (1991) Elevated plasma platelet-derived growth-factor-B-chain levels in cancer-patients. Cancer Res 51(16):4149–4154PubMedGoogle Scholar
  28. Liu X, Atwater M, Wang J, Huo Q (2007) Extinction coefficient of gold nanoparticles with different sizes and different capping ligands. Colloids Surf B Biointerfaces 58(1):3–7PubMedCrossRefGoogle Scholar
  29. Loo C, Lowery A, Halas N, West J, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5(4):709–711PubMedCrossRefADSGoogle Scholar
  30. Peres R, Betsholtz C, Westermark B, Heldin C-H (1987) Frequent expression of growth-factors for mesenchymal cells in human mammary-carcinoma cell-lines. Cancer Res 47(13):3425–3429PubMedGoogle Scholar
  31. Pernodet N et al (2006) Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small 2(6):766–773PubMedCrossRefGoogle Scholar
  32. Pissuwan D, Valenzuela SM, Cortie MB (2006) Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends Biotechnol 24(2):62–67PubMedCrossRefGoogle Scholar
  33. Proske D, Blank M, Buhmann R, Resch A (2005) Aptamers—basic research, drug development, and clinical applications. Appl Microbiol Biotechnol 69(4):367–374PubMedCrossRefGoogle Scholar
  34. Sokolov K et al (2003a) Optical systems for in vivo molecular imaging of cancer. Technol Cancer Res Treat 2(6):491–504PubMedGoogle Scholar
  35. Sokolov K et al (2003b) Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Res 63(9):1999–2004PubMedGoogle Scholar
  36. Storhoff JJ, Elghanian R, Mucic RC, Mirkin CA, Letsinger RL (1998) One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J Am Chem Soc 120(9):1959–1964CrossRefGoogle Scholar
  37. Thomas M, Klibanov AM (2003) Conjugation to gold nanoparticles enhances polyethylenimine’s transfer of plasmid DNA into mammalian cells. Proc Natl Acad Sci USA 100(16):9138–9143PubMedCrossRefADSGoogle Scholar
  38. Tkachenko AG et al (2003) Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. J Am Chem Soc 125(16):4700–4701PubMedCrossRefGoogle Scholar
  39. Tombelli S, Minunni M, Mascini M (2005) Analytical applications of aptamers. Biosens Bioelectron 20(12):2424–2434PubMedCrossRefGoogle Scholar
  40. Tsoli M, Kuhn H, Brandau W, Esche H, Schmid G (2005) Cellular uptake and toxicity of AU(55) clusters. Small 1(8–9):841–844PubMedCrossRefGoogle Scholar
  41. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment—rna ligands to bacteriophage-T4 DNA-polymerase. Science 249(4968):505–510PubMedCrossRefADSGoogle Scholar
  42. Yelin D, Oron D, Thiberge S, Moses E, Silberberg Y (2003) Multiphoton plasmon-resonance microscopy. Opt Express 11(12):1385–1391ADSCrossRefPubMedGoogle Scholar
  43. Yguerabide J, Yguerabide EE (1998) Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications: I. Theory Anal Biochem 262(2):137–156CrossRefGoogle Scholar
  44. Zhi PX, Qing HZ, Gao QL, Ai BY (2006) Inorganic nanoparticles as carriers for efficient cellular delivery. Chem Eng Sci 61(3):1027–1040CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Yu-Fen Huang
    • 1
  • Yang-Wei Lin
    • 1
  • Zong-Hong Lin
    • 1
  • Huan-Tsung Chang
    • 1
    • 2
  1. 1.Department of ChemistryNational Taiwan UniversityTaipeiTaiwan, ROC
  2. 2.Department of Natural Science EducationNational Taitung UniversityTaitungTaiwan, ROC

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