Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells. BMC Cancer 9:351

Chemical Science and Technology Laboratory, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA.
BMC Cancer (Impact Factor: 3.36). 10/2009; 9(1):351. DOI: 10.1186/1471-2407-9-351
Source: PubMed


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.
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.
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.
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.

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Available from: Xiugong Gao, Jan 07, 2015
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    • "Utilizing SWNTs functionalized by IGF1R and HER2 specific antibodies, Shao et al [40] observed only 20% viability of breast cancer cells after applying an 808 nm laser at 0.8 W cm −2 for 3 min. By using anti-HER2 lgY antibody functionalized SWNTs, Xiao et al [51] also achieved the selective destruction of breast cancer cells with SWNTs located on cancer cell membranes. Since photothermal therapy with NIR and CNTs is a promising effective cancer treatment, it is quintessentially important to quantitatively understand the photothermal energy conversion in the malignant tumor [27]. "
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    ABSTRACT: Single-walled carbon nanotubes (SWNTs) are promising heating agents in cancer photothermal therapy when under near infrared radiation, yet few efforts have been focused on the quantitative understanding of the photothermal energy conversion in biological systems. In this article, a mesoscopic study that takes into account SWNT morphologies (diameter and aspect ratio) and dispersions (orientation and concentration), as well as thermal boundary resistance, is performed by means of an off-lattice Monte Carlo simulation. Results indicate that SWNTs with orientation perpendicular to the laser, smaller diameter and better dispersion have higher heating efficiency in cancer photothermal therapy. Thermal boundary resistances greatly inhibit thermal energy transfer away from SWNTs, thereby affecting their heating efficiency. Through appropriate interfacial modification around SWNTs, compared to the surrounding healthy tissue, a higher temperature of the cancer cell can be achieved, resulting in more effective cancer photothermal therapy. These findings promise to bridge the gap between macroscopic and microscopic computational studies of cancer photothermal therapy.
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    • "Schematic illustration of functionalization of CNTs with various molecules: (a) Prakash et al. [18], (b) Xiao et al. [78], (c) Xu et al. [70], (d) Gomez-Gualdron et al. [64], (e) Bianco et al. [79], (f) Jiang et al. [80], (g) Williams et al. [81], and (h) Kam and Dai [82]. "
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    • "However in order to target the drug-loaded CNTs to the site of action, the surface of these materials need to be modified, preferably with the use of an antibody or a peptide (eg, anti-HER2 of the tubes to cancer cells). For example, since the number of folic acid receptors on the surface of the cancer cells increases, the presence of folic acid on CNT allows the tubes to be used to target cancer cells and enhance drug delivery.55 CNTs loaded with the anticancer drugs are injected into the circulation so that the antibody on the surface of the CNTs would direct these materials to the site of action.56 "
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