title: VEGFR-1 targeted DNAzyme via transcatheter arterial delivery influences tumor vasculature assessed through dynamic contrast-enhanced magnetic resonance imaging.
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.
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Interventional Radiology, Hospital of Finance and Commerce, Changsha, Hunan 410008, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D021881:DNA, Catalytic / Q000008:administration & dosage* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D065467:Transcatheter Aortic Valve Replacement / Q000379:methods; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D021881:DNA, Catalytic; D040281:Vascular Endothelial Growth Factor Receptor-1