Journal of Nanomedicine & Nanotechnology

Abstract

Nanogold-based Photosensitizers Probes for Dual-model Bioimaging and Therapy of Cancer

Jennifer M Connolly, Vijay Raghavan, Peter Owens, Antony Wheatley, Ivan Keogh, Peter Dockery and Malini Olivo

Reported here is the use of novel nanogold based photosensitisers (nanosensitisers) as optical diagnostic probes and as potential photodynamic and photothermal cancer therapeutic agents using an in vitro cancer cell model. Such multimodal nanosensitisers were constructed by layering photosensitisers (Hypericin, Chlorin e6) onto multi-branched gold nanoparticles. Nanosensitisers were conjugated to tumour-specific antibodies to confer cancer-cell specificity. Both oral (SCC9) and breast cancer (MCF7) cell lines were cultured in vitro with various concentrations of nanosensitisers. Cellular uptake and intracellular localisation of nanosensitisers was assessed using darkfield contrast imaging, transmission electron microscopy and Raman spectroscopy imaging and quantified using confocal fluorescence microscopy. In addition to photodynamic diagnosis (PDD) efficacy, the photodynamic (PDT) and photothermal (PTT) therapeutic potential of these novel nanosensitisers was assessed. Treated cells were exposed to light of appropriate wavelength and fluence, and cytotoxicity was examined using the 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. It was observed that nanosensitisers were taken up by cells and internalized. While the intracellular target of nanosensitisers appeared to be cell type-dependent, they were found to localise preferentially to lysosomes and mitochondria. The nanosensitisers were shown to exert minimal dark toxicity, and significant photodynamic-mediated cell death was observed in the micromolar concentration range (p<0.05). Results from this study suggest a celltype and photosensitiser-type dependence on the rate of nanosensitiser cellular uptake and intracellular distribution. This has a direct effect on photodynamic therapeutic efficacy of nanosenitisers. Biocompatibility of these novel gold nanosensitisers in vitro was demonstrated and the potential of such novel nanosensitisers as multifunctional optical agents for cancer diagnosis and therapy was highlighted. systems