Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
J Control Release. 2013 Aug 10;169(3):239-45. doi: 10.1016/j.jconrel.2013.01.034. Epub 2013 Feb 9.
Highly sensitive and safe contrast agents (CAs) are essential for magnetic resonance imaging (MRI) to achieve accurate tumor detection and imaging. Dendrimer-based macromolecular MRI contrast agents are advantageous owing to their tumor-targeting ability, enhanced imaging contrast and enlarged imaging window. However, most of them have drawbacks of non-degradability and thereby long-term retention in body and toxicity. Herein, a tumor-targeting biodegradable dendritic CA (DCA) (FA-PEG-G2-DTPA-Gd) was prepared from a polyester dendrimer conjugated with gadolinium (Gd) chelates and PEG chains with distal folic acid. The DCA had a high longitudinal relaxivity up to 17.1mM(-1)s(-1), 4 times higher than the clinically used CA Magnevist. The MRI contrasted by FA-PEG-G2-DTPA-Gd outlined the inoculated tumor more clearly, and had much higher contrast enhancement for a much longer time than Magnevist. More importantly, the biodegradable FA-PEG-G2-DTPA-Gd gave much less Gd retentions in all the organs or tissues than non-degradable DCAs. Thus, the high efficiency in MRI contrast enhancement and low Gd retention merit it a promising CA for contrast enhanced tumor MRI.
用于磁共振成像（MRI）的高灵敏度和安全的对比剂（CA）对于准确检测和成像肿瘤至关重要。基于树枝状大分子的高分子 MRI 对比剂具有肿瘤靶向能力、增强的成像对比度和扩大的成像窗口，因此具有优势。然而，它们中的大多数都存在不可降解性的缺点，从而导致在体内长期滞留和毒性。在此，我们制备了一种肿瘤靶向可生物降解的树枝状 CA（DCA）（FA-PEG-G2-DTPA-Gd），它是由与聚乙二醇链相连的具有远端叶酸的钆螯合物修饰的聚酯树枝状大分子组成的。该 DCA 的纵向弛豫率高达 17.1mM(-1)s(-1)，是临床使用的 CA Magnevist 的 4 倍。由 FA-PEG-G2-DTPA-Gd 进行的 MRI 对比可以更清晰地勾勒出接种的肿瘤，并且具有更高的对比增强效果，持续时间也更长。更重要的是，与不可降解的 DCA 相比，可生物降解的 FA-PEG-G2-DTPA-Gd 在所有器官或组织中的 Gd 滞留量要少得多。因此，它在 MRI 对比增强方面的高效性和低 Gd 滞留量使其成为一种很有前途的用于对比增强肿瘤 MRI 的 CA。
