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

Journal of Innovative Optical Health Sciences 2016年第4期9卷 55-65页

作者： Shuang Sha Fei Yang Anle Wang Honglin Jin Zhihong Zhang Qiaoya Lin Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics–Huazhong University of Science and Technology Wuhan 430074 P.R.China MoE Key Laboratory for Biomedical Photonics Department of Biomedical Engineering Huazhong University of Science and Technology Wuhan 430074 P.R.China

Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor biomarker.Metabolism investigation also plays important roles in tumor theranostics.Devel-oping 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 fuo-rescent probe Octa-R.GD by convenient genetic method,based on one tetrameric far-red fluo-rescent protein(frfp)linked with RGD pept ides.We validated its inter gin targeting by confocal imaging in vitro.Then we screened a variety of tumor cells,and differentiated their binding affinity based on the fuorescence 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 fuorescent and metabolic imaging was performed in HT1080(intergin postive)tumor,where nicotinamide adenine dinudeotide hydrogen(NADH),flavo-protein(Fp)and frfp fuorescent signals were collected.The tumor from mice intravenously injected with Octa RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH)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-R.GD probe facilitated its uptake in the targeted tumor in vrivo.This paper developed a useful probe,which can bind integrins speci-cally and e±ciently in tumor cells,and together with tumor metabolic information,it may provide new insight for RGD targeting-based cancer therapeutics.

关键词： Integrin redox metabolism frfp NADH Fp.

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