title: Herceptin-directed nanoparticles activated by an alternating magnetic field selectively kill HER-2 positive human breast cells in vitro via hyperthermia.
abstract: OBJECTIVE
  HER-2 is in the EGF tyrosine kinase receptor family, overexpressed by many human cancers and minimally expressed by normal adult tissues. HER-2 expression in human cancers is correlated with reduced survival, increased metastasis, reduced apoptosis and increased proliferation. Herceptin is a humanised mouse antibody that targets and inactivates HER-2. In the present study, Herceptin was used to deliver ferric oxide-enriched nanoparticles to HER-2(+) cancer cells. If exposed to alternating magnetic field (AMF), the nanoparticles heat. We tested the ability of AMF-activated Herceptin-directed nanoparticles to selectively kill HER-2(+) human cancer cells.
  
  
  METHODS
  Herceptin-conjugated nanoparticles were incubated with normal human mammary epithelial cells (HMEC)(HER-2(-)) or malignant human mammary epithelial cells (SK-BR-3)(HER-2(+)). Cells were stained to detect Herceptin or iron and the kinetics of binding quantified. Once conditions were optimised for binding, cells were exposed to either antibody-directed or non-antibody-conjugated nanoparticles, washed and sham-treated or exposed to AMF and cell death quantified.
  
  
  RESULTS
  SK-BR-3 cells bound Herceptin-directed nanoparticles in increasing amounts over 3 h but did not retain non-antibody conjugated nanoparticles. HMECs did not retain either nanoparticles. SK-BR-3 cells with bound Herceptin-directed-nanoparticles, exposed to AMF, died by apoptosis, quantifiable by Live/Dead and nuclear morphology assays and released LDH. Sham-treated SK-BR-3 cells with Herceptin-directed nanoparticles, HMECs with either nanoparticles, with or without AMF treatment, exhibited no increase in toxicity above baseline cell death using these three assays.
  
  
  CONCLUSIONS
  These studies demonstrate Herceptin-directed nanoparticles can selectively kill HER-2(+) cancer cells via hyperthermia after AMF activation.
authors: Department of Biological Sciences, University of Massachusetts, Lowell, MA 01854, USA.
authors: Jianping
authors: J
authors: Zhang
authors: Abiche H
authors: AH
authors: Dewilde
authors: Paul
authors: P
authors: Chinn
authors: Allan
authors: A
authors: Foreman
authors: Stephen
authors: S
authors: Barry
authors: David
authors: D
authors: Kanne
authors: Susan J
authors: SJ
authors: Braunhut
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D060526:Magnetic Fields; D053758:Nanoparticles / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005290:Ferric Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000499:ferric oxide