Journal of Neuro-Oncology

, Volume 104, Issue 1, pp 55–63 | Cite as

Nanoshell-mediated photothermal therapy improves survival in a murine glioma model

  • Emily S. Day
  • Patrick A. Thompson
  • Linna Zhang
  • Nastassja A. Lewinski
  • Nabil Ahmed
  • Rebekah A. Drezek
  • Susan M. Blaney
  • Jennifer L. West
Laboratory Investigation - Human/Animal Tissue

Abstract

We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica–gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-PrkdcSCID mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

Keywords

Glioma Nanoshells Thermal therapy Biodistribution Survival In vivo 

Supplementary material

11060_2010_470_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 kb)

References

  1. 1.
    Gladson CL, Prayson RA, Liu WM (2010) The pathobiology of glioma tumors. Annu Rev Pathol 5:33–50PubMedCrossRefGoogle Scholar
  2. 2.
    Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRefGoogle Scholar
  3. 3.
    Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507PubMedCrossRefGoogle Scholar
  4. 4.
    Daumas-Duport C, Scheithauer B, Ofallon J, Kelly P (1988) Grading of astrocytomas-a simple and reproducible method. Cancer 62(10):2152–2165PubMedCrossRefGoogle Scholar
  5. 5.
    Butler JM, Rapp SR, Shaw EG (2006) Managing the cognitive effects of brain tumor radiation therapy. Curr Treat Options Oncol 7(6):517–523PubMedCrossRefGoogle Scholar
  6. 6.
    Ricard D, Taillia H, Renard JL (2009) Brain damage from anticancer treatments in adults. Curr Opin Oncol 21(6):559–565PubMedCrossRefGoogle Scholar
  7. 7.
    Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag PM (2002) Hyperthermia in combined treatment of cancer. Lancet Oncol 3(8):487–497PubMedCrossRefGoogle Scholar
  8. 8.
    Day ES, Morton JG, West JL (2009) Nanoparticles for thermal cancer therapy. J Biomech Eng-Trans ASME 131(7):074001 (5 pp)Google Scholar
  9. 9.
    Maier-Hauff K, Rothe R, Scholz R, Gneveckow U, Wust P, Thiesen B, Feussner A, von Deimling A, Waldoefner N, Felix R, Jordan A (2007) Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme. J Neurooncol 81(1):53–60PubMedCrossRefGoogle Scholar
  10. 10.
    Wust P, Gneveckow U, Johannsen M, Bohmer D, Henkel T, Kahmann F, Sehouli J, Felix R, Ricke J, Jordan A (2006) Magnetic nanoparticles for interstitial thermotherapy—feasibility, tolerance and achieved temperatures. Int J Hyperth 22(8):673–685CrossRefGoogle Scholar
  11. 11.
    Jordan A, Scholz R, Maier-Hauff K, van Landeghem FKH, Waldoefner N, Teichgraeber U, Pinkernelle J, Bruhn H, Neumann F, Thiesen B, von Deimling A, Felix R (2006) The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol 78(1):7–14PubMedCrossRefGoogle Scholar
  12. 12.
    Dickerson EB, Dreaden EC, Huang XH, El-Sayed IH, Chu HH, Pushpanketh S, McDonald JF, El-Sayed MA (2008) Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. Cancer Lett 269(1):57–66PubMedCrossRefGoogle Scholar
  13. 13.
    Moon HK, Lee SH, Choi HC (2009) In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. ACS Nano 3(11):3707–3713PubMedCrossRefGoogle Scholar
  14. 14.
    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(2):171–176PubMedCrossRefGoogle Scholar
  15. 15.
    Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, West JL (2007) Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett 7(7):1929–1934PubMedCrossRefGoogle Scholar
  16. 16.
    Bernardi RJ, Lowery AR, Thompson PA, Blaney SM, West JL (2008) Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines. J Neurooncol 86(2):165–172PubMedCrossRefGoogle Scholar
  17. 17.
    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(23):13549–13554PubMedCrossRefGoogle Scholar
  18. 18.
    Oldenburg SJ, Averitt RD, Westcott SL, Halas NJ (1998) Nanoengineering of optical resonances. Chem Phys Lett 288(2–4):243–247CrossRefGoogle Scholar
  19. 19.
    Duff DG, Baiker A, Edwards PP (1993) A new hydrosol of gold clusters. 1. Formation and particle-size variation. Langmuir 9(9):2301–2309CrossRefGoogle Scholar
  20. 20.
    Ahmed N, Ratnayake M, Savoldo B, Perlaky L, Dotti G, Wels WS, Bhattacharjee MB, Gilbertson RJ, Shine HD, Weiss HL, Rooney CM, Heslop HE, Gottschalk S (2007) Regression of experimental medulloblastoma following transfer of her2-specific t cells. Cancer Res 67(12):5957–5964PubMedCrossRefGoogle Scholar
  21. 21.
    Loo C, Hirsch L, Lee MH, Chang E, West J, Halas N, Drezek R (2005) Gold nanoshell bioconjugates for molecular imaging in living cells. Opt Lett 30(9):1012–1014PubMedCrossRefGoogle Scholar
  22. 22.
    Loo C, Lowery A, Halas N, West J, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5(4):709–711PubMedCrossRefGoogle Scholar
  23. 23.
    Gobin AM, Moon JJ, West JL (2008) Ephrin AI-targeted nanoshells for photothermal ablation of prostate cancer cells. Int J Nanomed 3(3):351–358Google Scholar
  24. 24.
    De Jong WH, Hagens WI, Krystek P, Burger MC, Sips A, Geertsma RE (2008) Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29(12):1912–1919PubMedCrossRefGoogle Scholar
  25. 25.
    Sonavane G, Tomoda K, Makino K (2008) Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf B Biointerfaces 66(2):274–280PubMedCrossRefGoogle Scholar
  26. 26.
    Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, Katayama Y, Niidome Y (2006) Peg-modified gold nanorods with a stealth character for in vivo applications. J Control Release 114(3):343–347PubMedCrossRefGoogle Scholar
  27. 27.
    Xie H, Gill-Sharp KL, O’Neal DP (2007) Quantitative estimation of gold nanoshell concentrations in whole blood using dynamic light scattering. Nanomedicine 3(1):89–94PubMedGoogle Scholar
  28. 28.
    James WD, Hirsch LR, West JL, O’Neal PD, Payne JD (2007) Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice. J Radioanal Nucl Chem 271(2):455–459CrossRefGoogle Scholar
  29. 29.
    DeAngelis LM (2001) Brain tumors. N Engl J Med 344(2):114–123PubMedCrossRefGoogle Scholar
  30. 30.
    Lowery AR, Gobin AM, Day ES, Halas NJ, West JL (2006) Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomed 1(2):149–154CrossRefGoogle Scholar
  31. 31.
    Schwartz JA, Shetty AM, Price RE, Stafford RJ, Wang JC, Uthamanthil RK, Pham K, McNichols RJ, Coleman CL, Payne JD (2009) Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model. Cancer Res 69(4):1659–1667PubMedCrossRefGoogle Scholar
  32. 32.
    ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29-[updated 2010 Feb 2; cited 2010 Sept 9]. Identifier NCT00848042, pilot study of AuroLase™ therapy in refractory and/or recurrent tumors of the head and neck, 4 pp. http://clinicaltrials.gov/ct2/show/NCT00848042

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Emily S. Day
    • 1
  • Patrick A. Thompson
    • 2
  • Linna Zhang
    • 2
  • Nastassja A. Lewinski
    • 1
  • Nabil Ahmed
    • 2
  • Rebekah A. Drezek
    • 1
  • Susan M. Blaney
    • 2
  • Jennifer L. West
    • 1
  1. 1.Department of BioengineeringRice UniversityHoustonUSA
  2. 2.Texas Children’s Cancer CenterTexas Children’s Hospital, Baylor College of MedicineHoustonUSA

Personalised recommendations