Method for Enhancing Cell Penetration of Gd3+-based MRI Contrast Agents by Conjugation with Hydrophobic Fluorescent Dyes

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• 作者：Takehiro Yamane ; Kenjiro Hanaoka ; Yasuaki Muramatsu ; Keita Tamura ; Yusuke Adachi ; Yasushi Miyashita ; Yasunobu Hirata ; Tetsuo Nagano
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：November 16, 2011
• 年：2011
• 卷：22
• 期：11
• 页码：2227-2236
• 全文大小：514K
• 年卷期：v.22,no.11(November 16, 2011)
• ISSN：1520-4812

文摘

Gadolinium ion (Gd³⁺) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T₁-weighted MR images. Recently, several methods to achieve cell-permeation of Gd³⁺ complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell permeation of Gd³⁺ complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd³⁺ complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell permeability and dye structure, we further synthesized a series of Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd³⁺ complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd³⁺ complexes, and should be applicable for further development of Gd³⁺-based MRI contrast agents.