Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines
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.
KeywordsBiophotonics Glioma HER2 Interluekin-13 receptor Medulloblastoma Nanoshells Nanotechnology Near infrared
- 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
- 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