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Application of Gold Nanorods in Cancer Theranostics
Mohan Singh*1, Elham Nabavi1, Yu Zhou2,1, Hailin Zhao3, Daqing Ma3, Anthony Cass2, George B. Hanna1, Daniel Elson1
1Hamlyn Centre for Robotic Surgery, Department of Surgery & Cancer, Imperial College London, Birmingham, United Kingdom; 2Department of Chemistry, Imperial College London, London, United Kingdom; 3Department of Anaesthetics, Imperial College London, London, United Kingdom
Introduction
Gold nanoparticles can be utilised as photothermal therapeutic agents because of their strongly enhanced absorption of the near infrared light (NIR) region resulting in hyperthermia induced by their surface plasmon resonance. We investigate the fluorescence-guided photothermal effect from gold nanorods (GNRs) in the diagnostics and therapy (theranostics) of in vivo upper gastrointestinal adenocarcinoma.
Methods
Coated gold nanorods (GNRs) were functionalised with a fluorophore (Cy5.5 dye) modified with anti-EGFR antibody. Tumour xenografts were established in immunodeficient mice by subcutaneous inoculation of human oesophageal adenocarcinoma (FLO-1) cells. Once tumours attained treatment size, functionalised GNRs were then randomised to be administered either intratumourally (IT) or intravenously (IV) into mice. Fluorescence imaging was performed to observe tumour site contrast enhancement, followed by tumour irradiation by an 808 nm (NIR) continuous wave laser for three minutes. A thermal imaging camera recorded the temperature changes that occurred during irradiation. Inductively coupled plasma mass spectrometry (ICP-MS) measured the concentration of gold within blood and organs after 30 days. Control mice with tumours received either IT/IV GNRs or laser alone.
Results
Functionalised GNRs had a peak optical absorption at 808 nm. In vivo, bright fluorescence emissions were observed specifically from the tumour sites, providing critical diagnostic information. Subsequent NIR irradiation established clinically significant hyperthermia in tumours receiving both IV and IT GNRs. This photothermal effect resulted in the successful ablation of tumours which was confirmed histopathologically 30 days post-irradiation. ICP-MS revealed no evidence of harmful accumulation of gold in all organs. No behavioural changes, morbidity or weight loss was observed. Control mice continued to harbour aggressive tumours.
Conclusion
This study examines the theranostic potential of GNRs on adenocarcinoma in vivo, which has a place in both early and late stage cancers. Fluorescence imaging of GNRs that localise to cancerous tissue enhances cancer diagnosis. When coupled with a single short delivery of NIR light, this minimally invasive and clinically translatable technique can safely and effectively produce irreversible tumour photodestruction. Providing an alternative means of cancer theranostics that is cheap, rapid and effective can instigate significant improvements in prognosis, treatment and quality of life.
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