Journal of Innovative Optical Health Sciences, 2016, 9 (4): 1642002, Published Online: Dec. 27, 2018  

Fluorescent and quantitative mitochondrial redox imaging of tumor targeted by Octa-RGD probe

Author Affiliations
1 Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics–Huazhong University of Science and Technology Wuhan 430074, P. R. China
2 MoE Key Laboratory for Biomedical Photonics Department of Biomedical Engineering Huazhong University of Science and Technology Wuhan 430074, P. R. China
Abstract
Integrins, over-expressed in a broad range of cancer diseases, are widely utilized as a tumor biomarker. Metabolism investigation also plays important roles in tumor theranostics. Developing simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment, however, the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so far. Here, we developed an octavalent fluorescent probe Octa-RGD by convenient genetic method, based on one tetrameric far-red fluorescent protein (fRFP) linked with RGD peptides. We validated its intergin targeting by confocal imaging in vitro. Then we screened a variety of tumor cells, and differentiated their binding affinity based on the fluorescence of the probe via flow cytometry. Among these cells, CNE-2 cells had the highest uptake of the probe, while B16 cells had the lowest, corresponding with their intergin expression levels. Next, the fluorescent and metabolic imaging was performed in HT1080 (intergin postive) tumor, where nicotinamide adenine dinucleotide hydrogen (NADH), flavoprotein (Fp) and fRFP fluorescent signals were collected. The tumor from mice intravenously injected with Octa-RGD probe displayed obviously higher NADH redox ratio NADH/ (FptNADH) and fRFP signal, than those with fRFP protein. It suggested that integrin targeting may have influence on the target cell metabolism, and further demonstrated Octa-RGD probe facilitated its uptake in the targeted tumor in vivo. This paper developed a useful probe, which can bind integrins specifically and efficiently in tumor cells, and together with tumor metabolic information, it may provide new insight for RGD targeting-based cancer therapeutics.

Shuang Sha, Fei Yang, Anle Wang, Honglin Jin, Zhihong Zhang, Qiaoya Lin. Fluorescent and quantitative mitochondrial redox imaging of tumor targeted by Octa-RGD probe[J]. Journal of Innovative Optical Health Sciences, 2016, 9(4): 1642002.

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