Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity
Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity
复制标题
DOI：
10.1021/acs.biomac.5b01668
复制
发表时间：
2016-04-01
影响因子：
6.2
通讯作者：
Angelovski, Goran
中科院分区：
文献类型：
--
作者：
Garello, Francesca;Vibhute, Sandip;Angelovski, Goran
对Ca（II）波动敏感的生物响应MRI造影剂可能在功能性分子成像方法的发展中发挥关键作用，以研究大脑生理学或肌肉收缩异常。其化学中的一个巨大挑战是制备能够诱导可以以稳健的方式检测到的强信号变化的探针。为此，将小分子量生物响应剂掺入纳米载体中可以以几种方式改善总体性质：（i）该试剂可以递送到感兴趣的组织中，增加局部浓度;（ii）其生物动力学性质和保留时间将改善;（iii）其生物动力学性质和保留时间将改善。（iii）纳米载体的高分子量和尺寸可能会导致MRI信号的额外变化，并增加在功能实验中检测到它们的机会。在这项工作中，我们报告了一类新的脂质体为基础的，钙敏感的MRI剂的制备。我们合成了一种新型的两亲性配体，并将其整合到脂质体双层膜中。最具活性的脂质体制剂分别在25 ℃和21.5 MHz下，在不存在和存在Ca（II）的情况下，纵向弛豫率r（1）从7.3 mM（-1）s（-1）显著增加至38.1 mM（-1）s（-1），增加幅度接近420%。据我们所知，这是在生理pH值下观察到的Ca敏感剂的r1的最高变化，并且可以通过同时Ca触发的水合作用增加和Gd（III）络合物的局部运动减少来解释，这可以在低磁场下进行。
Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in the development of functional molecular imaging methods to study brain physiology or abnormalities in muscle contraction. A great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation that could be detected in a robust way. To this end, the incorporation of small molecular weight bioresponsive agents into nanocarriers can improve the overall properties in a few ways: (i) the agent can be delivered into the tissue of interest, increasing the local concentration; (ii) its biokinetic properties and retention time will improve; (iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesized a novel amphiphilic ligand which was incorporated into the liposome bilayer. A remarkable increase of similar to 420% in longitudinal relaxivity r(1), from 7.3 mM(-1) s(-1) to 38.1 mM(-1) s(-1) at 25 degrees C and 21.5 MHz in the absence and presence of Ca(II), respectively, was achieved by the most active liposomal formulation. To the best of our knowledge, this is the highest change in r1 observed for Ca-sensitive agents at physiological pH and can be explained by simultaneous Ca-triggered increase in hydration and reduction of local motion of Gd(III) complex, which can be followed at low magnetic fields.