VEGFR-1 targeted DNAzyme via transcatheter arterial delivery influences tumor vasculature assessed through dynamic contrast-enhanced magnetic resonance imaging

Zhang,Liqing; Zhao,Wei; Liang,Chen; Yi,Xiaoping; Pei,Yigang; Lin,Yiting; He,Jiang; Li,Wenzheng

doi:10.3892/or.2016.4933

VEGFR-1 targeted DNAzyme via transcatheter arterial delivery influences tumor vasculature assessed through dynamic contrast-enhanced magnetic resonance imaging

Authors:
- Liqing Zhang
- Wei Zhao
- Chen Liang
- Xiaoping Yi
- Yigang Pei
- Yiting Lin
- Jiang He
- Wenzheng Li
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Affiliations: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Interventional Radiology, Hospital of Finance and Commerce, Changsha, Hunan 410008, P.R. China, Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: July 12, 2016 https://doi.org/10.3892/or.2016.4933
Pages: 1339-1344

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Abstract

DNAzymes are synthetic single-stranded DNA oligonucleotides that bind and cleave target mRNA in a sequence-specific manner. Although the therapeutic potential has been demonstrated in both preclinical and clinical settings, the efficient delivery and in vivo assessment of the DNAzyme efficacy remain the vital unsolved issue. In the present study, we examined the feasibility of using transcatheter arterial chemoembolization (TACE) strategy to deliver a DNAzyme targeting VEGFR-1 and monitoring its effect on tumor angiogenesis in vivo via dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). In a rabbit liver cancer model (VX2), we showed that the DNAzyme was efficiently delivered into the tumor by TACE. DCE-MRI revealed that the VEGFR-1-targeted DNAzyme affected the tumor vasculature through inhibiting VEGFR-1 expression in vivo, which was reflected by a reduction of Ktrans and Kep, the parameters of tumor microvascular permeability. Our findings offer an efficient strategy of delivery and assessment of the VEGFR-1 DNAzyme, and further demonstrate the feasibility of DNAzyme for cancer therapy.

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