Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent
Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent
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肽缀合聚酰胺胺树状聚合物作为纳米级肿瘤靶向 T1 磁共振成像造影剂
DOI：
10.1016/j.biomaterials.2011.01.005
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发表时间：
2011-04-01
期刊：
影响因子：
14
通讯作者：
Jiang, Chen
中科院分区：
文献类型：
--
作者：
Han, Liang;Li, Jianfeng;Jiang, Chen
研究了一种肿瘤靶向载体，肽HAIYPRH （T7）共轭聚乙二醇修饰聚氨基胺树突状物（PAMAM-PEG-T7），用于特异性靶向肿瘤细胞递送磁共振成像（MRI）造影剂。选择两种不同类型的肿瘤，肝癌和早期脑胶质瘤模型（涉及血脑屏障），评估该造影剂的成像能力。合成PAMAM-PEG-T7，与二乙烯三胺五乙酸（DTPA）偶联，再与钆（Gd）螯合，得到GdDTPA-PAMAM-PEG-T7。ICP-AES结果表明，每个PAMAM分子可装载约92个Gd离子。计算得到GdDTPA-PAMAM- peg - t7的纵向弛度R1为10.7 mm(-1) S-1 / Gd (984.4 mm(-1) S-1 / PAMAM)，而GdDTPA的纵向弛度R1仅为4.8 mm(-1) S-1。与PAMAM-PEG相比，PAMAM-PEG- t7在体外和体内对肝癌细胞具有更好的靶向能力。PAMAM-PEG- t7的积累量是PAMAM-PEG的162.5%。但对于胶质瘤细胞，PAMAM-PEG-T7没有表现出特异性。此外，GdDTPA-PAMAM-PEG- t7可以通过增强信号提高肝癌的诊断效率（187%），而PAMAM-PEG为130%，GdDTPA为121%。GdDTPA-PAMAM-PEG-T7可选择性鉴别肝癌，但不能鉴别早期胶质瘤。这种纳米级MRI造影剂GdDTPA-PAMAM-PEG-T7可能允许选择性和有效地诊断没有天然屏障的肿瘤，包括肝癌。(C) 2011 Elsevier Ltd.版权所有。
A tumor-targeting carrier, peptide HAIYPRH (T7)-conjugated polyethylene glycol-modified polyamidoamine dendrimer (PAMAM-PEG-T7) was explored to deliver magnetic resonance imaging (MRI) contrast agents targeting to the tumor cells specifically. Two different types of tumors, liver cancer and early brain glioma model (involved with the blood-brain barrier), were chosen to evaluate the imaging capacity of this contrast agent. PAMAM-PEG-T7 was synthesized, conjugated with diethylene triamine pentaacetic acid (DTPA) and further chelated gadolinium (Gd), yielding GdDTPA-PAMAM-PEG-T7. The result of ICP-AES showed that about 92 Gd ions could be loaded per PAMAM molecule. The calculated longitudinal relaxivity R1 of the GdDTPA-PAMAM-PEG-T7 was 10.7 mm(-1) S-1 per Gd (984.4 mm(-1) S-1 per PAMAM), while that of GdDTPA was only 4.8 mm(-1) S-1. PAMAM-PEG-T7 had better targeting capacity to the liver cancer cells in vitro and in vivo, compared with PAMAM-PEG. The accumulation of PAMAM-PEG-T7 was 162.5% times that of PAMAM-PEG. But for glioma cells, PAMAM-PEG-T7 did not show its specificity. Furthermore, GdDTPA-PAMAM-PEG-T7 could improve the diagnostic efficiency of liver cancer with the enhanced signal (187%), compared to 130% for PAMAM-PEG and 121% for GdDTPA. GdDTPA-PAMAM-PEG-T7 could selectively identify liver cancer but not early glioma. This nanoscaled MRI contrast agent GdDTPA-PAMAM-PEG-T7 might allow for selective and efficient diagnosis of tumors without the natural barrier including liver cancer. (C) 2011 Elsevier Ltd. All rights reserved.