Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent.
Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent.
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DOI：
10.1002/anie.200905133
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发表时间：
2010
影响因子：
16.6
通讯作者：
Tsourkas, Andrew
中科院分区：
文献类型：
--
作者：
Cheng, Zhiliang;Thorek, Daniel L. J.;Tsourkas, Andrew
造影剂越来越多地用于诊断磁共振 (MR) 成像，以帮助检测和表征病理异常。事实上，据估计，近 50% 的 MR 检查已经涉及使用 MR 造影剂，其中螯合钆化合物是迄今为止使用最广泛的。[1, 2] 大多数临床相关的钆基制剂都是小型非靶向化合物，它们被动分布到血管内和间质空间中。[3]然而，最近人们对开发顺磁性造影剂产生了兴趣，这些造影剂能够通过配体靶向、酶活性和多重检测来探测组织的分子谱。 [4, 5] 预计这些试剂可用于获得更具体的临床诊断，从而改善患者管理。为了补偿单个 Gd 离子产生的低信号增强，大多数靶向 Gd 化合物依赖于纳米平台的开发，该纳米平台可以 (1) 携带高负载的 Gd 和 (2) 增强纵向弛豫率 (R1)，每 Gd。多种大分子和其他纳米颗粒系统已经作为 Gd 标记平台进行了测试，包括树枝状聚合物、[6–12] 聚合物、[13] 乳液、[14] 二氧化硅纳米颗粒、[15–17] 和囊泡。[18–21] 其中一些试剂表现出每个纳米颗粒 105 至 106 mM− 1 s− 1 数量级的弛豫率。 [14, [17, 18] 由于当连接到这些纳米颗粒载体时，螯合 Gd 的 R1 通常仅在 5 至 30 mM− 1 s− 1 之间，因此这些造影剂显然受益于其携带高 Gd 有效负载的能力。此外，由于 Gd 的理论最大 R1 估计仅为约 80 mM− 1 s− 1 (1.5 T)，[22] 可以说，未来每个粒子 R1 的任何重大改进都将通过开发支持更高 Gd 有效负载的纳米平台来实现。考虑到目前大多数纳米平台仅在其外表面上用 Gd 螯合物标记，为了确保高水可及性，我们假设通过开发在整个颗粒内体积中含有高 Gd 含量的高度多孔纳米颗粒可以实现更高的 Gd 有效负载。在这里，我们表明，这可以通过创建由单个 Gd 标记的 PAMAM 树枝状聚合物组成的“树枝状聚合物纳米簇”（DNC）来实现，这些树枝状聚合物已交联形成更大的纳米颗粒载体。我们还证明，这些 Gd 标记的 DNC 可以很容易地用靶向配体（例如叶酸）进行功能化，并用于体内分子生物学
Contrast agents are increasingly being used in diagnostic magnetic resonance (MR) imaging to help detect and characterize pathological abnormalities. In fact, it has been estimated that nearly 50% of all MR examinations already involve the use of MR contrast agents, with chelated gadolinium compounds being by far the most widely used.[1, 2] Most clinically relevant Gd-based agents are small, non-targeted compounds that passively distribute into the intravascular and interstitial space.[3] However, there has recently been emerging interest in the development of paramagnetic contrast agents that are capable of probing the molecular profile of tissues via ligand targeting, enzymatic activity and multiplexing.[4, 5] It is envisioned that these agents could be used to acquire a more specific clinical diagnosis and thus improve patient management.To compensate for the low signal enhancement generated by individual Gd ions, most targeted Gd compounds have relied on the development of nanoplatforms that can (1) carry a high payload of Gd and (2) enhance the longitudinal relaxivities (R1), per Gd. A wide range of macromolecules and other nanoparticulate systems have already been tested as platforms for Gd labeling, including dendrimers,[6–12] polymers,[13] emulsions,[14] silica nanoparticles,[15–17] and vesicles.[18–21] Some of these agents have exhibited relaxivities on the order of 105 to 106 mM− 1 s− 1 per nanoparticle.[14, 17, 18] Since the R1 for chelated Gd is typically only between 5 and 30 mM− 1 s− 1 when attached to these nanoparticulate carriers, these contrast agents clearly benefited most from their ability to carry a high Gd payload. Further, since the theoretical maximum R1 for Gd is estimated to be only~ 80 mM− 1 s− 1 (1.5 T),[22] it can be argued that any major future improvements in the R1 per particle will be achieved through the development of nanoplatforms that support higher Gd payloads. Considering that most current nanoplatforms are only labeled with Gd chelates on their outer surface, to ensure high water accessibility, we hypothesized that higher Gd payloads could be achieved through the development of highly porous nanoparticles that contained a high Gd content throughout the intraparticular volume. Here, we show that this could be accomplished by creating “dendrimer nanoclusters”(DNCs) composed of individual Gd-labeled PAMAM dendrimers that have been cross-linked to form larger nanoparticulate carriers. We also demonstrate that these Gd-labeled DNCs can readily be functionalized with targeting ligands (eg folic acid) and used for in vivo molecular
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影响因子：
5.5
作者：
Jackson, CL;Chanzy, HD;Amis, EJ
通讯作者：
Amis, EJ
影响因子：
2.9
作者：
Langereis, S;de Lussanet, QG;Backes, WH
通讯作者：
Backes, WH
影响因子：
4.7
作者：
Rudovsky, Jakub;Botta, Mauro;Aime, Silvio
通讯作者：
Aime, Silvio
影响因子：
3.3
作者：
Morawski, AM;Winter, PM;Wickline, SA
通讯作者：
Wickline, SA
影响因子：
29.4
作者：
Santra, S;Bagwe, RP;Mericle, RA
通讯作者：
Mericle, RA