Monitoring phospholipase A₂ activity with Gd-encapsulated phospholipid liposomes.

Monitoring phospholipase A₂ activity with Gd-encapsulated phospholipid liposomes.
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DOI:
10.1038/srep06958
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发表时间:
2014-11-07
期刊:
影响因子:
4.6
通讯作者:
Tsourkas A
Tsourkas A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cheng Z;Tsourkas A

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到目前为止,已经开发了许多分析方法来监测磷脂酶A2(PLA2)的活性。然而,这些方法中的许多需要使用可能改变酶动力学的非天然PLA2底物,以及不能扩展到更复杂环境中的应用的探针。开发一种基于与复杂生物样品中的天然磷脂相互作用来监测PLA2活性的通用方法是可取的。在这里,我们开发了一种可激活的T1磁共振(MR)成像造影剂来监测PLA2的活性。具体地说,临床批准的基于Gd的磁共振造影剂加多特罗被包裹在纳米尺寸的磷脂脂质体中。由于膜通透性低,包裹的Gd显示出低T1加权信号。然而,当磷脂膜中的磷脂被PLA2水解时,包裹的Gd被释放到本体溶液中,导致T1-松弛时间发生了明显的变化。这些可激活的磁共振造影剂有可能被用作纳米传感器,以最少的样品制备来监测生物样品中PLA2的活性。
To date, numerous analytical methods have been developed to monitor phospholipase A2 (PLA2) activity. However, many of these methods require the use of unnatural PLA2 substrates that may alter enzyme kinetics, and probes that cannot be extended to applications in more complex environments. It would be desirable to develop a versatile assay that monitors PLA2 activity based on interactions with natural phospholipids in complex biological samples. Here, we developed an activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2 activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast agent, gadoteridol, was encapsulated within nanometer-sized phospholipid liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low membrane permeability. However, when the phospholipids within the liposomal membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk solution, resulting in a measureable change in the T1-relaxation time. These activatable MR contrast agents can potentially be used as nanosensors for monitoring of PLA2 activity in biological samples with minimal sample preparation.
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