National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
Biomaterials. 2011 Apr;32(10):2575-85. doi: 10.1016/j.biomaterials.2010.12.049. Epub 2011 Jan 21.
The quest for highly efficient and safe contrast agents has become the key factor for successful application of magnetic resonance imaging (MRI). The gadolinium (Gd) based dendritic macromolecules, with precise and tunable nanoscopic sizes, are excellent candidates as multivalent MRI probes. In this paper, a novel series of Gd-based multifunctional peptide dendritic probes (generation 2, 3, and 4) possessing highly controlled structures and single molecular weight were designed and prepared as liver MRI probes. These macromolecular Gd-ligand agents exhibited up to 3-fold increase in T(1) relaxivity comparing to Gd-DTPA complexes. No obvious in vitro cytotoxicity was observed from the measured concentrations. These dendritic probes were further functionalized with multiple galactosyl moieties and led to much higher cell uptake in vitro as demonstrated in T(1)-weighted scans. During in vivo animal studies, the probes provided better signal intensity (SI) enhancement in mouse liver, especially at 60 min post-injection, with the most efficient enhancement from the galactosyl moiety decorated third generation dendrimer. The imaging results were verified with analysis of Gd content in liver tissues. The design strategy of multifunctional Gd-ligand peptide dendritic macromolecules in this study may be used for developing other sensitive MRI probes with targeting capability.
寻找高效、安全的对比剂已成为磁共振成像（MRI）成功应用的关键因素。基于钆（Gd）的树枝状大分子，具有精确可调的纳米尺寸，是多价 MRI 探针的理想候选物。本文设计并制备了一系列新型基于 Gd 的多功能肽树枝状探针（第 2、3 和 4 代），作为肝脏 MRI 探针，具有高度可控的结构和单一分子量。这些高分子 Gd-配体与 Gd-DTPA 复合物相比，T1 弛豫率提高了 3 倍。从测量的浓度来看，没有观察到明显的体外细胞毒性。这些树枝状探针进一步功能化多个半乳糖基部分，导致体外细胞摄取率大大提高，如 T1 加权扫描所示。在体内动物研究中，探针在小鼠肝脏中提供了更好的信号强度（SI）增强，特别是在注射后 60 分钟，带有半乳糖基部分的第三代树枝状大分子的增强效果最为明显。成像结果通过对肝组织中 Gd 含量的分析得到验证。本研究中多功能 Gd-配体肽树枝状大分子的设计策略可用于开发具有靶向能力的其他敏感 MRI 探针。
