Abstract
Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice. Using both orthotopic tumour transplantation and cirrhosis models in parallel, we demonstrated the ability of DZ-1 to differentiate liver tumour from cirrhosis. DZ-1 showed superiority in HCC imaging over indocyanine green by demonstrating significantly enhanced tumour-targeting specificity. At the cellular level, DZ-1 was mainly retained in mitochondria and lysosomes. Additionally, DZ-1 fluorescence spectroscopy has been used for the intraoperative navigation of rabbit liver cancer, to determine surgical margins. We showed that tumor hypoxia and select organic anion-transporting polypeptide genes mediate NIRF dye uptake in HCC, which was supported by clinical evidence. All these findings represent the first evidence that DZ-1 is an effective molecular probe for tumour-specific imaging in HCC, and provide insights into the development of a new generation of imaging agents for intraoperative guidance of cancer surgery.
Highlights
Near-infrared fluorescence (NIRF) wavelengths (700-1,000 nm) are attractive for potential biomedical applications due to their increased penetration depth and decreased scattering and absorption in tissues relative to the ultraviolet and visible wavelengths [1]
We showed that tumor hypoxia and select organic anion-transporting polypeptide genes mediate NIRF dye uptake in hepatocellular carcinoma (HCC), which was supported by clinical evidence
To determine NIRF DZ-1 dye uptake by tumour cells in vivo, subcutaneous tumour xenografts of Hep3B-Luc cells were established in the nude mice
Summary
Near-infrared fluorescence (NIRF) wavelengths (700-1,000 nm) are attractive for potential biomedical applications due to their increased penetration depth and decreased scattering and absorption in tissues relative to the ultraviolet and visible wavelengths [1]. NIRF dyes display strong signal strength, and their chemical modifications can improve the stability of molecular groups and trigger strong fluorescence emission for the use in imaging-based cancer diagnostics [2,3,4]. These dyes represent good molecular probes and are used widely in animal and human imaging studies [5,6,7,8]. ICG-based tumour www.impactjournals.com/oncotarget imaging often involves non-specific delivery of the dye to tissues other than tumour sites [9,10,11,12]
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