Introduction Gold nanoparticles possess unique physiochemical properties due to their ability to target cancerous tissue and a strongly enhanced absorption of visible and near infra-red (NIR) light resulting in hyperthermia and photothermal therapy (PTT). Fluorescence emission from their functionalised surface provides diagnostic information regarding tumour location. Their biocompatibility in vivois facilitated through surface polymer coating. We investigate these properties in human oesophageal adenocarcinoma by examining in vitro targeting of functionalised gold nanorods to human oesophageal adenocarcinoma cells (FLO-1) and evaluating the PTT of tumour xenografts in vivo .
Method Multifunctional coated gold nanorods (GNRs) were fabricated using a seed-mediated method. Subsequent EDC/NHS chemistry functionalised the GNRs with a fluorophore (Cy 5.5) modified with anti-EGFR antibody.
FLO-1 cells were fixed in paraformaldehyde in 0.1 mol/l PBS solution. Dilute functionalised GNRs were added and incubated overnight. Slides were then washed with PBS and stained with the nuclear dye DAPI prior to microscopic examination.
Tumour xenografts were established in immunodeficient mice by subcutaneous inoculation of FLO-1 cells. When tumour size reached 5 mm, functionalized GNRs were administered either intratumourally (I. T.) or intravenously (I. V.). Fluorescence spectroscopy was performed followed by NIR irradiation of the tumour for 3 min using an 808 nm laser at 0.92 W. A thermal imaging camera measured the temperature changes that occurred. Inductively coupled plasma mass spectrometry (ICP-MS) measured gold concentrations in blood and organs remote to the tumour.
Results Functionalised GNRs with a peak optical absorption at 808 nm were used. Fluorescence imaging of immunohistochemically stained FLO-1 cells demonstrated active in vitro targeting of GNRs.
NIR irradiation of tumours established 12°C and 18°C temperature increases in mice receiving I. V. and I. T. GNRs respectively. Histological examination of tumour sites showed fully preserved tissue layers with no signs of proliferating tumour. ICP-MS revealed no evidence of toxic accumulation of gold in blood, kidneys, liver or spleen after 30 days.
Conclusion Fluorescence detection of functionalised GNRs that localise to cancerous tissue may enhance oesophageal cancer diagnosis. When coupled with NIR irradiation, this is an effective method of inducing irreversible tumour photodestruction, with minimal collateral damage expected in healthy tissues. The strong absorption of GNRs of relatively low laser energies renders the therapy method minimally invasive.
Disclosure of interest None Declared.
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