Novel pH-sensitive paramagnetic liposomes with improved MR properties
Novel pH-sensitive paramagnetic liposomes with improved MR properties
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DOI：
10.1002/mrm.20009
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发表时间：
2004-04-01
影响因子：
3.3
通讯作者：
Fossheim, SL
中科院分区：
文献类型：
--
作者：
Lokling, KE;Skurtveit, R;Fossheim, SL
使用顺磁性pH敏感的脂质体最近建议作为一种新的方法来监测病理变化的pH值的MRI。这样的脂质体必须在血液中稳定，并且当暴露于靶组织中的较低pH时选择性地释放包封的顺磁性剂。在本研究中，不同的脂质体系统的制定和弛豫，低温透射电子显微镜（cryo-TEM），和MRI的特点。pH敏感系统二棕榈酰磷脂酰乙醇胺/棕榈酸（DPPE/PA）脂质体GdDTPA-BMA，这是以前被证明是不稳定的血液中，修改，以提高其稳定性。胆固醇掺入DPPE/PA脂质体显着增加其在血液中的稳定性，但pH敏感性降低。聚乙二醇修饰的DPPE/PA脂质体在缓冲液中对pH不敏感，在血液中不稳定。然而，用双链两亲物二棕榈酰甘油琥珀酸酯（DPSG）交换PA产生具有改善性质的脂质体。DPPE/DPSG脂质体GdDTPA-BMA在生理pH下在血液中稳定，并显示出显著的pH敏感性。在血液中预孵育后的pH值的敏感性并没有减少，相反，已报道的类似物含有不饱和脂质。在体外MRI体模研究中证明了该系统监测pH值的潜力。(C)2004 Wiley-Liss，Inc.
The use of paramagnetic pH-sensitive liposomes was recently suggested as a new approach for monitoring pathologic changes in pH by MRI. Such liposomes must be stable in blood and selectively release the encapsulated paramagnetic agent when exposed to lower pH in the target tissue. In the present study, different liposomal systems were formulated and characterized by relaxometry, cryo-transmission electron microscopy (cryo-TEM), and MRI. The pH-sensitive system dipalmitoylphosphatidylethanolamine/palmitic acid (DPPE/PA) liposomal GdDTPA-BMA, which was previously shown to be unstable in blood, was modified to improve its stability. The incorporation of cholesterol into the DPPE/PA liposomes significantly increased their stability in blood, but the pH sensitivity was diminished. Polyethylene glycol (PEG)-modified DPPE/PA liposomes were pH-insensitive in buffer, and unstable in blood. However, exchanging PA with the double-chained amphiphile dipalmitoylglycerosuccinate (DPSG) yielded liposomes with improved properties. DPPE/DPSG liposomal GdDTPA-BMA was stable in blood at physiological pH, and displayed a marked pH sensitivity. The pH sensitivity was not diminished after preincubation in blood, contrary to what has been reported for analogues containing unsaturated lipids. The potential of this System for monitoring pH was demonstrated in an in vitro MRI phantom study. (C) 2004 Wiley-Liss, Inc.