Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange
Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange
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DOI：
10.1021/ja0158455
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发表时间：
2001-09-05
影响因子：
15
通讯作者：
van Zijl, PCM
中科院分区：
文献类型：
--
作者：
Goffeney, N;Bulte, JWM;van Zijl, PCM
阳离子聚合物（CP）作为非病毒DNA递送系统在基因治疗中的潜在用途变得越来越重要。1因此，如果能够以足够的灵敏度检测低浓度的这些化合物，以允许体内基因递送或抗体靶向的非侵入性可视化，则将是有用的。为了使用MRI实现这一点，必须用（超）顺磁性标记物标记这些化合物，2-4然而，添加金属标记物通常很麻烦，并且可能增加递送系统的总体毒性。利用酰胺质子的固有性质，迅速与水交换，我们表明，灵敏度的提高高达500，000的因素是可能的，允许检测微摩尔浓度的大分子与水的摩尔灵敏度。这一结果表明，一个新的家庭的非顺磁性大分子MRI造影剂的对比度的基础上存在的多个水可访问的酰胺基团的可能性。
Cationic polymers (CPs) have become increasingly important as nonviral DNA delivery systems for potential use in gene therapy. 1 As such, it would be useful if low concentrations of these compounds could be detected with sufficient sensitivity to allow noninvasive visualization of gene delivery or antibody targeting in vivo. To accomplish this using MRI, it has been necessary to label these compounds with (super) paramagnetic tags, 2-4 However, the addition of metallic labels is often cumbersome and may increase the overall toxicity of the delivery systems. Exploiting the inherent properties of amide protons that rapidly exchange with water, we show that enhancements in sensitivity by factors as large as 500,000 are possible, allowing the detection of micromolar concentrations of macromolecules with the molar sensitivity of water. This result suggests the possibility of a new family of nonparamagnetic macromolecular MRI contrast agents with contrast based on the presence of multiple water-accessible amide groups.