Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging
Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging
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DOI：
10.1021/bc7001715
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发表时间：
2008-01-01
影响因子：
4.7
通讯作者：
Miller, Andrew D.
中科院分区：
文献类型：
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作者：
Kamaly, Nazila;Kalber, Tammy;Miller, Andrew D.
介绍了一种用于细胞标记的新型双峰荧光顺磁性脂质体。在这项研究中，我们展示了一种新的Gd脂质的合成，Gd.DOTA.DSA，设计用于脂质体细胞标记和肿瘤成像。为了最大限度地允许细胞进入，对由这种脂质组成的脂质体配方进行了优化，并将优化后的配方用于体外标记HeLa细胞。用荧光显微镜和磁共振成像(MRI)证明了这种新型双峰Gd-脂质体制剂用于细胞标记的效率。细胞摄取Gd-脂质体后，其核磁共振T弛豫时间显著缩短。荧光显微镜提供了摄取的伴随证据，并显示脂质体内化到细胞胞浆中。优化的处方也显示出最小的细胞毒性，并被证明具有质粒DNA(PDNA)的转染力。进一步描述了第二种新型中性双峰Gd-脂质体，用于标记体内移植瘤，利用增强的渗透和保留效应(EPR)。将IGROV-1细胞接种于BALB/c裸鼠，用低电荷的体内Gd脂质体和聚乙二醇长体循环的催化剂对肿瘤进行MRI成像。MRI显示这些直径小于100 nm的Gd脂质体聚集在肿瘤组织中，组织学标本的荧光显微镜也证实了这一点。我们的体内肿瘤成像结果证明了MRI的有效性，它可以实时观察长期循环脂质体对肿瘤的被动靶向，并允许MRI指导治疗，其中可以监控治疗基因和药物到肿瘤部位的输送，同时可以观察、量化和关联对肿瘤质量和/或大小的治疗效果。
A novel bimodal fluorescent and paramagnetic liposome is described for cellular labeling. In this study, we show the synthesis of a novel gadolinium lipid, Gd.DOTA.DSA, designed for liposomal cell labeling and tumor imaging. Liposome formulations consisting of this lipid were optimized in order to allow for maximum cellular entry, and the optimized formulation was used to label HeLa cells in vitro. The efficiency of this novel bimodal Gd-liposome formulation for cell labeling was demonstrated using both fluorescence microscopy and magnetic resonance imaging (MRI). The uptake of Gd-liposomes into cells induced a marked reduction in their MRI T, relaxation times. Fluorescence microscopy provided concomitant proof of uptake and revealed liposome internalization into the cell cytosol. The optimized formulation was also found to exhibit minimal cytotoxicity and was shown to have capacity for plasmid DNA (pDNA) transfection. A further second novel neutral bimodal Gd-liposome is described for the labeling of xenograft tumors in vivo utilizing the enhanced permeation and retention effect (EPR). Balb/c nude mice were inoculated with IGROV-1 cells, and the resulting, tumor was imaged by MRI using these in vivo Gd-liposomes formulated with low charge and a poly(ethylene glycol) (PEG) calyx for long systemic circulation. These Gd-liposomes which were less than 100 nm in size were shown to accumulate in tumor tissue by MRI, and this was also verified by fluorescence microscopy of histology samples. Our in vivo tumor imaging results demonstrate the effectiveness of MRI to observe passive targeting of long-term circulating liposomes to tumors in real time, and allow for MRI directed therapy, wherein the delivery of therapeutic genes and drugs to tumor sites can be monitored while therapeutic effects on tumor mass and/or size may be simultaneously observed, quantitated, and correlated.