Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Biomaterials. 2011 Apr;32(11):2989-98. doi: 10.1016/j.biomaterials.2011.01.005. Epub 2011 Jan 28.
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.
一种肿瘤靶向载体，即肽 HAIYPRH（T7）- 聚乙二醇修饰的聚酰胺胺树枝状大分子（PAMAM-PEG-T7），被探索用于专门靶向肿瘤细胞递送磁共振成像（MRI）造影剂。选择了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），来评估这种造影剂的成像能力。合成了 PAMAM-PEG-T7，与二亚乙基三胺五乙酸（DTPA）缀合，进一步螯合钆（Gd），得到 GdDTPA-PAMAM-PEG-T7。ICP-AES 的结果表明，每个 PAMAM 分子可以负载约 92 个 Gd 离子。GdDTPA-PAMAM-PEG-T7 的计算纵向弛豫率 R1 为每个 Gd 为 10.7 mm-1 S-1（每个 PAMAM 为 984.4 mm-1 S-1），而 GdDTPA 仅为 4.8 mm-1 S-1。与 PAMAM-PEG 相比，PAMAM-PEG-T7 具有更好的肝癌细胞体外和体内靶向能力。PAMAM-PEG-T7 的积累是 PAMAM-PEG 的 162.5%。但对于神经胶质瘤细胞，PAMAM-PEG-T7 并没有表现出其特异性。此外，与 PAMAM-PEG（130%）和 GdDTPA（121%）相比，GdDTPA-PAMAM-PEG-T7 可以提高肝癌的诊断效率（187%）。GdDTPA-PAMAM-PEG-T7 可以选择性地识别肝癌，而不是早期神经胶质瘤。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肿瘤，而无需包括肝癌在内的天然屏障。
