Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics.
Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics.
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DOI：
10.1016/j.nano.2011.03.007
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发表时间：
2011-12
影响因子：
5.4
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
--
作者：
Kojima, Chie;Turkbey, Baris;Ogawa, Mikako;Bernardo, Marcelino;Regino, Celeste A. S.;Bryant, L. Henry, Jr.;Choyke, Peter L.;Kono, Kenji;Kobayashi, Hisataka
聚乙二醇（PEG）表面修饰可以使纳米材料高度亲水，减少在网状内皮系统中的隔离。在这项研究中，聚酰胺胺（PAMAM）树枝状大分子轴承钆螯合物PEG化与不同的PEG链长度和顺磁性和药代动力学特性的影响进行了评价。具体地，将带有钆螯合物的PAMAM树枝状聚合物（G4和G5）与两个不同的PEG链（2k和5 k）缀合。与未PEG化的树枝状聚合物相比，较小（G4）树枝状聚合物上的长PEG链（5 k）导致弛豫率降低，而短PEG（2k）和较大（G5）树枝状聚合物产生与未PEG化的G4树枝状聚合物相当的弛豫率。所有PEG化或赖氨酸缀合的树枝状聚合物的弛豫率在较高的温度下增加，而完整的G4 Gd-PAMAM-树枝状聚合物的弛豫率降低。所有PEG化的树枝状聚合物具有最小的肝脏和肾脏摄取，并在循环中保持至少1小时。因此，表面PEG化的Gd-PAMAM-树枝状聚合物显示出降低的血浆清除率和延长的在血池中的保留。PEG越短，代数越高，弛豫率越高。
Polyethylene glycol (PEG)-surface modification can make nano-materials highly hydrophilic, reducing sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium chelates were PEGylated with different PEG-chain lengths and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, gadolinium chelate-bearing PAMAM dendrimers (G4 and G5) were conjugated with two different PEG chains (2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to unPEGylated dendrimer whereas short PEG (2k) and larger (G5) dendrimer produced comparable relaxivities to unPEGylated G4 dendrimer. The relaxivity of all PEGylated or lysine conjugated dendrimers increased at higher temperature, while that of intact G4 Gd-PAMAM-dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM-Dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led higher relaxivity.
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通讯作者：
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