Nanoshell-mediated photothermal therapy improves survival in a murine glioma model
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.
KeywordsGlioma Nanoshells Thermal therapy Biodistribution Survival In vivo
- 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.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
- 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
- 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
- 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