Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents.
Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents.
复制标题
DOI：
10.1016/j.jconrel.2009.01.010
复制
发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
K. Shiraishi;K. Kawano;T. Minowa;Y. Maitani;M. Yokoyama
中科院分区：
文献类型：
--
作者：
K. Shiraishi;K. Kawano;T. Minowa;Y. Maitani;M. Yokoyama
聚合物胶束药物载体系统被应用于 MRI（磁共振成像）造影剂的靶向。嵌段共聚物 PEG-b-聚（L-赖氨酸）用于通过螯合部分 DOTA 缀合钆离子。 DOTA 部分成功地与赖氨酸残基的所有伯胺基团缀合。所得嵌段共聚物PEG-b-聚(L-赖氨酸-DOTA)形成聚合物胶束。即使在部分钆螯合（~40%）到 DOTA 部分后，聚合物胶束结构仍保持不变。将制备好的聚合物胶束 MRI 造影剂以 0.05 mmol Gd/kg 的剂量注射到小鼠尾静脉中。基于聚合物胶束的MRI造影剂表现出稳定的血液循环。通过 EPR 效应，静脉注射后 24 小时，发现大量物质（6.1±0.3% ID/g 聚合物胶束）在实体瘤中积聚。 MRI 分析显示，使用这种造影剂后，肿瘤的信号强度增强了 2.0 倍。
A polymeric micelle drug carrier system was applied to the targeting of an MRI (magnetic resonance imaging) contrast agent. A block copolymer, PEG-b-poly(L-lysine), was used for conjugation of gadolinium ions through chelating moieties, DOTA. The DOTA moieties were successfully conjugated to all primary amine groups of the lysine residues. The obtained block copolymer, PEG-b-poly(L-lysine-DOTA), formed a polymeric micelle. The polymeric micelle structure was maintained even after partial gadolinium chelation (∼40%) to the DOTA moieties. The prepared polymeric micelle MRI contrast agent was injected into a mouse tail vein at a dose of 0.05 mmol Gd/kg. The polymeric micelle-based MRI contrast agent exhibited stable blood circulation. A considerable amount (6.1±0.3% of ID/g of the polymeric micelle) was found to accumulate at solid tumors 24 h after intravenous injection by means of the EPR effect. An MRI analysis revealed that the signal intensity of the tumor was enhanced 2.0-fold by the use of this contrast agent.