Accepted manuscript
Near-infrared fluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis
Biomaterials, Vol.35(28), pp.8175-8185
09/2014
PMCID: PMC4180424
PMID: 24957295
Abstract
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 1α (HIF1α). 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 HIF1α 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 HIF1α/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.
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Details
- Title
- Near-infrared fluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis
- Creators
- Jason Boyang Wu - Washington State University, Pharmaceutical Sciences, Department ofChen Shao - Fourth Military Medical UniversityXiangyan Li - Cedars-Sinai Medical CenterChanghong Shi - Cedars-Sinai Medical CenterQinlong Li - Xijing HospitalPeizhen Hu - Cedars-Sinai Medical CenterYi-Ting Chen - Cedars-Sinai Medical CenterXiaoliang Dou - Fourth Military Medical UniversityDivya Sahu - University of Southern CaliforniaWei Li - Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USAHiroshi Harada - Kyoto UniversityYi Zhang - Cedars-Sinai Medical CenterRuoxiang Wang - Cedars-Sinai Medical CenterHaiyen E Zhau - Cedars-Sinai Medical CenterLeland W.K Chung - Cedars-Sinai Medical Center
- Publication Details
- Biomaterials, Vol.35(28), pp.8175-8185
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900620489101842
- Language
- English
- Resource Type
- Accepted manuscript