title: Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: an in vitro evaluation using human cell lines.
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 (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.
authors.affiliation: Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bernardi
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Lowery
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Thompson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems / Q000379:methods; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D007259:Infrared Rays; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology / Q000378:metabolism; D007834:Lasers; D008527:Medulloblastoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D053758:Nanoparticles / Q000528:radiation effects / Q000627:therapeutic use*; D010789:Phototherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured