Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.
Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.
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DOI：
10.1016/j.biomaterials.2012.09.070
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发表时间：
2013-01
期刊：
影响因子：
14
通讯作者：
Tabor AB
中科院分区：
文献类型：
--
作者：
Mitchell N;Kalber TL;Cooper MS;Sunassee K;Chalker SL;Shaw KP;Ordidge KL;Badar A;Janes SM;Blower PJ;Lythgoe MF;Hailes HC;Tabor AB
设计并合成了一系列金属螯合脂质结合物。该系列的每个成员都带有一个1，4，7，10-tetraazacyclododecane-1，4，7，10-tetraacetic酸(DOTA)大环，连接到脂头基团上，使用不同长度的短正乙二醇(n-EG)间隔物。将这些脂类与Gd3+、64Cu2+或111In3+进行络合，并加入荧光脂类，制备了脂质体，并研究了它们在体外和体内细胞摄取和分布的光学、磁共振(MR)和单光子发射断层扫描(SPECT)成像中的应用。我们已经证明，这些多模式脂质体可以用作功能性磁共振造影剂以及SPECT的放射性核素示踪剂，并且它们可以根据不同的应用进行优化。当屏蔽脂质体含有50%的脂质和较短的n-EG间隔物，以提供覆盖浅但均匀的n-EG的纳米颗粒时，它们在一系列肿瘤细胞中表现出良好的细胞内化作用，而传统的含有7%1，2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)2000]的屏蔽脂质体的细胞摄取有限(DSPE-PEG2000)。此外，通过将n-EG的覆盖深度与DOTA脂类的n-EG间隔物的长度进行匹配，我们已经表明，可以获得与DSPE-PEG2000稳定的脂质体相似的分布和血液半衰期。调整这些脂质体的成像性能和分布的能力为未来开发灵活的三模式显像剂奠定了基础。
A series of metal-chelating lipid conjugates has been designed and synthesized. Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these lipids, chelated to Gd3+, 64Cu2+, or 111In3+, and also incorporating fluorescent lipids, have been prepared, and their application in optical, magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of cellular uptake and distribution investigated in vitro and in vivo. We have shown that these multimodal liposomes can be used as functional MR contrast agents as well as radionuclide tracers for SPECT, and that they can be optimized for each application. When shielded liposomes were formulated incorporating 50% of a lipid with a short n-EG spacer, to give nanoparticles with a shallow but even coverage of n-EG, they showed good cellular internalization in a range of tumour cells, compared to the limited cellular uptake of conventional shielded liposomes formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)2000] (DSPE-PEG2000). Moreover, by matching the depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we have shown that similar distributions and blood half lives to DSPE-PEG2000-stabilized liposomes can be achieved. The ability to tune the imaging properties and distribution of these liposomes allows for the future development of a flexible tri-modal imaging agent.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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