Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, UKSW7 2AZ.
Org Biomol Chem. 2010 Jan 7;8(1):201-11. doi: 10.1039/b910561a. Epub 2009 Nov 5.
We have synthesized a bimodal lipidic molecule bearing both fluorophore and contrast agent signatures on the same structure in order to create a robust bimodal liposome for both magnetic resonance imaging (MRI) and fluorescence microscopy utility. The dual-modality concept considered in the synthesis of this new paramagnetic and fluorescent lipid is valuable in that anatomical information (MRI) as well as very sensitive localization (ex vivo fluorescence microscopy) of signal, and therefore liposome biodistribution, is obtainable. Bimodal cationic and neutral PEGylated liposomes were formulated using this novel lipid probe and used to label cells in vitro and image human ovarian xenografts in vivo. Tumour signal enhancement was increased by over 6-fold post-administration of the neutral PEGylated liposomes, and was maintained at this level up to the 24 h end-point. Our results showed this lipid to be more effective and sensitive than the single signature paramagnetic lipid Gd.DOTA.DSA at cellular labelling and tumour MRI.
我们合成了一种双模脂质分子,在同一结构上同时具有荧光团和对比剂的特征,以便为磁共振成像 (MRI) 和荧光显微镜的应用创建一种稳健的双模脂质体。在合成这种新的顺磁和荧光脂质时考虑的双模概念在以下方面具有价值:可以获得解剖信息 (MRI) 以及信号的非常灵敏的定位(离体荧光显微镜),因此可以获得脂质体的生物分布。使用这种新型脂质探针制备了双模阳离子和中性聚乙二醇化脂质体,并用于体外标记细胞和体内成像人卵巢异种移植物。中性聚乙二醇化脂质体给药后,肿瘤信号增强超过 6 倍,并保持在该水平,直到 24 小时终点。我们的结果表明,与单标记顺磁脂质 Gd.DOTA.DSA 相比,该脂质在细胞标记和肿瘤 MRI 方面更有效和更敏感。