title: Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells.
abstract: Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specificity of the nanoshells for HER2+ breast cancer. Silica-gold nanoshells conjugated with anti-HER2 were incubated with both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells. Nanoshell binding was confirmed using two-photon laser scanning microscopy, and the cells were then ablated using a near-infrared laser. We demonstrate the successful targeting and ablation of trastuzumab-resistant cells using anti-HER2-conjugated silica-gold nanoshells and a near-infrared laser. This study suggests potential for applying gold nanoshell-mediated therapy to trastuzumab-resistant breast cancers in vivo.
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main St., MS-142, Houston, TX 77005, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Carpin
authors.forename: Lissett R
authors.initials: LR
authors.lastname: Bickford
authors.forename: Germaine
authors.initials: G
authors.lastname: Agollah
authors.forename: Tse-Kuan
authors.initials: TK
authors.lastname: Yu
authors.forename: Rachel
authors.initials: R
authors.lastname: Schiff
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Drezek
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006046:Gold; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D053685:Laser Therapy; D018613:Microscopy, Confocal; D057145:Nanoshells; D010789:Phototherapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006046:Gold; D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab