Near-infrared fluorescence imaging of cancer mediated by tumor hypoxia and HIFI alpha/OATPs signaling axis BIOMATERIALS Wu, J. B., Shao, C., Li, X., Shi, C., Li, Q., Hu, P., Chen, Y., Dou, X., Sahu, D., Li, W., Harada, H., Zhang, Y., Wang, R., Zhau, H. E., Chung, L. W. 2014; 35 (28): 8175-8185


Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the mechanistic properties of a specific group of NIR heptamethine carbocyanines including MHI-148 dye we identified and synthesized, and demonstrated these dyes to achieve cancer-specific imaging and targeting via a hypoxia-mediated mechanism. We found that cancer cells and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake in vitro and in vivo, which was directly mediated by hypoxia-inducible factor 1a (HIF1a). Microarray analysis and dye uptake assay further revealed a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) responsible for dye uptake, and the correlation between OATPs and HIF1a was manifested in progressive clinical cancer specimens. Finally, we demonstrated increased uptake of MHI-148 dye in situ in perfused clinical tumor samples with activated HIF1a/OATPs signaling. Our results establish these NIRF dyes as potential tumor hypoxia-dependent cancer-targeting agents and provide a mechanistic rationale for continued development of NIRF imaging agents for improved cancer detection, prognosis and therapy.

View details for DOI 10.1016/j.biomaterials.2014.05.073

View details for Web of Science ID 000339774700012

View details for PubMedID 24957295