Mulder Willem J M, Strijkers Gustav J, van Tilborg Geralda A F, Griffioen Arjan W, Nicolay Klaas
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
NMR Biomed. 2006 Feb;19(1):142-64. doi: 10.1002/nbm.1011.
In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed.
在磁共振成像领域，特别是在新兴的细胞与分子磁共振成像领域，需要灵活的策略来合成造影剂，这些造影剂在尺寸和组成方面能够被调控，并且能够轻松地与靶向配体结合。此外，造影剂的弛豫率，尤其是对于分子成像应用而言，应该非常高，以应对磁共振成像的低灵敏度。基于脂质的纳米颗粒，如脂质体或胶束，在近几十年中被广泛用作药物载体。脂质纳米颗粒一个相对较新且有前景的应用是用作多模态磁共振造影剂。脂质是具有疏水和亲水部分的两亲性分子，它们在水性环境中会自发聚集形成聚集体。在这些聚集体中，两亲分子的排列方式使得疏水部分聚集在一起，而亲水部分面向水。在低浓度状态下，可以形成多种结构，从球形胶束到盘状或脂质体。此外，单层脂质可以作为外壳包裹疏水核心。疏水性氧化铁颗粒、量子点或全氟碳乳液都可以通过这种方法进行增溶。可被磁共振检测且具有荧光性的两亲性分子能够轻松地掺入脂质纳米颗粒中。此外，通过掺入带有功能基团的脂质，可以将靶向配体与脂质颗粒结合，从而实现与分子标志物的特异性相互作用，并使颗粒在疾病部位积累。在本综述中，给出了用于磁共振成像的不同脂质纳米颗粒的概述，主要重点是基于钆的造影剂。讨论了颗粒形成的机制、结合策略以及在对比增强、细胞及分子磁共振成像领域的应用。
