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 (IL13Ralpha2), 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 IL13Ralpha2, U373 and U87, but not in A431 epidermoid carcinoma cells that do not express significant levels of IL13Ralpha2. 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.

Immunonanoshells for targeted photothermal ablation of tumor cells.

Consisting of a silica core surrounded by a thin gold shell, nanoshells possess an optical tunability that spans the visible to the near infrared (NIR) region, a region where light penetrates tissues deeply. Conjugated with tumor-specific antibodies, NIR-absorbing immunonanoshells can preferentially bind to tumor cells. NIR light then heats the bound nanoshells, thus destroying the targeted cells. Antibodies can be consistently bound to the nanoshells via a bifunctional polyethylene glycol (PEG) linker at a density of approximately 150 antibodies per nanoshell. In vitro studies have confirmed the ability to selectively induce cell death with the photothermal interaction of immunonanoshells and NIR light. Prior to incubation with anti-human epidermal growth factor receptor (HER2) immunonanoshells, HER2-expressing SK-BR-3 breast carcinoma cells were seeded alone or adjacent to human dermal fibroblasts (HDFs). Anti-HER2 immunonanoshells bound to HER2-expressing cells resulted in the death of SK-BR-3 cells after NIR exposure only within the irradiated area, while HDFs remained viable after similar treatment since the immunonanoshells did not bind to these cells at high levels. Control nanoshells, conjugated with nonspecific anti-IgG or PEG, did not bind to either cell type, and cells continued to be viable after treatment with these control nanoshells and NIR irradiation.