Herceptin-directed nanoparticles activated by an alternating magnetic field selectively kill HER-2 positive human breast cells in vitro via hyperthermia.
Int J Hyperthermia
; 27(7): 682-97, 2011.
Article
em En
| MEDLINE
| ID: mdl-21992561
ABSTRACT
PURPOSE:
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Nanopartículas
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Anticorpos Monoclonais Humanizados
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Campos Magnéticos
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Hipertermia Induzida
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article