Abstract
BackgroundNanocarrier-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.MethodsThe 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.ResultsUsing 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.ConclusionWe 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.
Highlights
Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology
We have demonstrated that the HER2 IgY-Single-walled carbon nanotube (SWNT) complex 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
Summary
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. Nanomedicine, an emerging research area that integrates nanomaterials and biomedicine, has the potential to provide novel diagnostic tools for detection of primary cancers at their earliest stages, and to provide improved therapeutic protocols. Attaching antibodies or other targeting agents (such as receptor ligands) to the surface of nanocarriers to achieve specific targeting of cancerous cells is a promising modality for therapeutic and diagnostic oncology [1]. Improved therapeutic efficacy of targeted nanocarriers has been established in multiple animal models of cancer, and currently more than 120 clinical trials are underway with various antibody-containing nanocarrier formulations [2]. Recent developments in nanotechnology have engendered a range of novel inorganic nanomaterials, such as metal nanoshells [3] and carbon nanotubes [4], offering unique opto-electronic properties compared with conventional organic nanocarriers [3,4]
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