Journal of Neuro-Oncology

, Volume 86, Issue 2, pp 165–172 | Cite as

Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines

  • Ronald J. Bernardi
  • Amanda R. Lowery
  • Patrick A. Thompson
  • Susan M. Blaney
  • Jennifer L. West
lab investigation - human/animal tissue

Abstract

We are developing a novel approach to specifically target malignant brain tumor cells for photothermal ablation using antibody-tagged, near infrared-absorbing gold-silica nanoshells, referred to as immunonanoshells. Once localized to tumor cells, these nanoshells are extremely efficient at absorbing near-infrared light and can generate sufficient heat to kill cancer cells upon exposure to laser light. In this study, we evaluated the efficacy of immunonanoshells in vitro against both medulloblastoma and high-grade glioma cell lines. We used an antibody against HER2 to target gold-silica nanoshells to medulloblastoma cells, since HER2 is frequently overexpressed in medulloblastoma. We show that treatment with HER2-targeted nanoshells, but not non-targeted nanoshells, followed by exposure to laser light, can induce cell death in the HER2-overexpressing medulloblastoma cell line Daoy.2, as well as the parental Daoy cell line, which expresses HER2 at a moderate level, but not in dermal fibroblasts that do not express HER2. In an analogous set of experiments, we conjugated gold-silica nanoshells to an antibody against interleukin-13 receptor-alpha 2 (IL13Rα2), an antigen that is frequently overexpressed in gliomas. We demonstrate that these immunonanoshells are capable of inducing cell death in two high-grade glioma cell lines that express IL13Rα2, U373 and U87, but not in A431 epidermoid carcinoma cells that do not express significant levels of IL13Rα2. We believe that the use of antibody-tagged gold-silica nanoshells to selectively target cancer cells presents a promising new strategy for the treatment of central nervous system tumors that will minimize the damage and resulting toxicity to the surrounding normal brain.

Keywords

Biophotonics Glioma HER2 Interluekin-13 receptor Medulloblastoma Nanoshells Nanotechnology Near infrared 

Bibliography

  1. 1.
    Hirsch LR, Gobin AM, Lowery AR, Tam F, Drezek RA, Halas NJ, West JL (2006) Metal nanoshells. Ann Biomed Eng 34:15–22PubMedCrossRefGoogle Scholar
  2. 2.
    Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–317PubMedCrossRefGoogle Scholar
  3. 3.
    McBride G (2002) Studies expand potential uses of photodynamic therapy. J Natl Cancer Inst 94:1740–1742PubMedGoogle Scholar
  4. 4.
    Muller PJ, Wilson BC (2006) Photodynamic therapy of brain tumors-a work in progress. Lasers Surg Med 38:384–389PubMedCrossRefGoogle Scholar
  5. 5.
    Eljamel MS (2003) New light on the brain: the role of photosensitizing agents and laser light in the management of invasive intracranial tumors. Technol Cancer Res Treat 2:303–309PubMedGoogle Scholar
  6. 6.
    Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle JD, Halas NJ, West JL (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci USA 100:13549–13554PubMedCrossRefGoogle Scholar
  7. 7.
    Maeda H, Fang J, Inutsuka T, Kitamoto Y (2003) Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int Immunopharmacol 3:319–328PubMedCrossRefGoogle Scholar
  8. 8.
    O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL (2004) Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett 209:171–176PubMedCrossRefGoogle Scholar
  9. 9.
    Lowery AR, Gobin AM, Day ES, Halas NJ, West JL (2006) Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomedicine 1:149–154PubMedCrossRefGoogle Scholar
  10. 10.
    Hernan R, Fasheh R, Calabrese C, Frank AJ, Maclean KH, Allard D, Barraclough R, Gilbertson RJ (2003) ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res 63:140–148PubMedGoogle Scholar
  11. 11.
    Gilbertson R, Wickramasinghe C, Hernan R, Balaji V, Hunt D, Jones-Wallace D, Crolla J, Perry R, Lunec J, Pearson A, Ellison D (2001) Clinical and molecular stratification of disease risk in medulloblastoma. Br J Cancer 85:705–712PubMedCrossRefGoogle Scholar
  12. 12.
    Gajjar A, Hernan R, Kocak M, Fuller C, Lee Y, McKinnon PJ, Wallace D, Lau C, Chintagumpala M, Ashley DM, Kellie SJ, Kun L, Gilbertson RJ (2004) Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22:984–993PubMedCrossRefGoogle Scholar
  13. 13.
    Ray A, Ho M, Ma J, Parkes RK, Mainprize TG, Ueda S, McLaughlin J, Bouffet E, Rutka JT, Hawkins CE (2004) A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res 10:7613–7620PubMedCrossRefGoogle Scholar
  14. 14.
    Press MF, Cordon-Cardo C, Slamon DJ (1990) Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5:953–962PubMedGoogle Scholar
  15. 15.
    Kawakami M, Kawakami K, Takahashi S, Abe M, Puri RK (2004) Analysis of interleukin-13 receptor alpha2 expression in human pediatric brain tumors. Cancer 101:1036–1042PubMedCrossRefGoogle Scholar
  16. 16.
    Mintz A, Gibo DM, Slagle-Webb B, Christensen ND, Debinski W (2002) IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13. Neoplasia 4:388–399PubMedCrossRefGoogle Scholar
  17. 17.
    Kioi M, Husain SR, Croteau D, Kunwar S, Puri RK (2006) Convection-enhanced delivery of interleukin-13 receptor-directed cytotoxin for malignant glioma therapy. Technol Cancer Res Treat 5:239–250PubMedGoogle Scholar
  18. 18.
    Eguchi J, Hatano M, Nishimura F, Zhu X, Dusak JE, Sato H, Pollack IF, Storkus WJ, Okada H (2006) Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responses. Cancer Res 66:5883–5891PubMedCrossRefGoogle Scholar
  19. 19.
    Zhou G, Roizman B (2006) Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13alpha2 receptor. Proc Natl Acad Sci USA 103:5508–5513PubMedCrossRefGoogle Scholar
  20. 20.
    Oldenburg SJ, Averitt RD, Westcott SL, Halas NJ (1998) Nanoengineering of optical resonances. Chem Phys Lett 288:243–247CrossRefGoogle Scholar
  21. 21.
    Stober W, Fink A, Bohn E (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26:62–69CrossRefGoogle Scholar
  22. 22.
    Duff DG, Baiker A, Edwards P (1993) A new hydrosol of gold clusters. 1. Formation and particle size variation. Langmuir 9:2301–2309CrossRefGoogle Scholar
  23. 23.
    Sathornsumetee S, Rich JN (2006) New approaches to primary brain tumor treatment. Anti-cancer drugs 17:1003–1016PubMedCrossRefGoogle Scholar
  24. 24.
    Butowski NA, Sneed PK, Chang SM (2006) Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol 24:1273–1280PubMedCrossRefGoogle Scholar
  25. 25.
    Mulhern RK, Palmer SL (2003) Neurocognitive late effects in pediatric cancer. Curr Probl Cancer 27:177–197PubMedCrossRefGoogle Scholar
  26. 26.
    Jakacki RI (2005) Treatment strategies for high-risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Review of the literature. J Neurosurg 102:44–52PubMedGoogle Scholar
  27. 27.
    Broniscer A (2006) Past, present, and future strategies in the treatment of high-grade glioma in children. Cancer Invest 24:77–81PubMedCrossRefGoogle Scholar
  28. 28.
    Liu T, Cai J, Gibo DM, Debinski W (2007) A variant of interleukin 13 fused to diphtheria toxin is selectively cytotoxic to glioblastoma multiforme cells. In: 2007 American Association for Cancer Research Annual Meeting Proceedings, April 14–18, 2007, Los Angeles, CA. Philadelphia, PA, AACR Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ronald J. Bernardi
    • 1
  • Amanda R. Lowery
    • 2
  • Patrick A. Thompson
    • 1
  • Susan M. Blaney
    • 1
  • Jennifer L. West
    • 2
  1. 1.Texas Children’s Cancer CenterTexas Children’s Hospital, Baylor College of MedicineHoustonUSA
  2. 2.Department of BioengineeringRice UniversityHoustonUSA

Personalised recommendations