Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells.
BACKGROUND
Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells.


METHODS
The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm2 for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining.


RESULTS
Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously.


CONCLUSIONS
We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy.
Chemical Science and Technology Laboratory, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA. yan.xiao@nist.gov
Yan
Y
Xiao
Xiugong
X
Gao
Oleh
O
Taratula
Stephen
S
Treado
Aaron
A
Urbas
R David
RD
Holbrook
Richard E
RE
Cavicchi
C Thomas
CT
Avedisian
Somenath
S
Mitra
Ronak
R
Savla
Paul D
PD
Wagner
Sudhir
S
Srivastava
Huixin
H
He
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D037742:Nanotubes, Carbon / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000627:therapeutic use*; D013059:Spectrum Analysis, Raman
D007136:Immunoglobulins; D037742:Nanotubes, Carbon; D018719:Erb-b2 Receptor Tyrosine Kinases; C016512:IgY; C508053:ERBB2 protein, human