Cheng Zhiliang, Tsourkas Andrew
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Langmuir. 2008 Aug 5;24(15):8169-73. doi: 10.1021/la801027q. Epub 2008 Jun 21.
The ability of chelated Gd to serve as an effective magnetic resonance (MR) contrast agent largely depends on fast exchange rates between the Gd-bound water molecules and the surrounding bulk water. Because water diffuses slowly across lipid bilayers, liposomes with encapsulated chelated Gd have not been widely adopted as MR contrast agents. To overcome this limitation, we have synthesized chemically stabilized, porous polymersomes with encapsulated gadolinium (Gd) chelates. The polymerosmes, 125 nm in diameter, were produced from the aqueous assembly of diblock copolymers, PEO(1300)- b-PBD(2500) (PBdEO), and phospholipids, 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC). The PBdEO was cross-linked using a chemical initiator and the POPC was extracted with surfactant, generating a highly porous outer membrane. The encapsulated Gd chelates were attached to dendrimers to prevent their leakage through the pores. It was estimated that, on average, nearly 44 000 Gd were encapsulated within each polymersome. As a result of the slower rotational correlation time of Gd-labeled dendrimers and the porous outer membrane, the paramagnetic porous polymersomes exhibited an R1 relaxivity of 7.2 mM (-1) s (1-) per Gd and 315 637 mM (-1) s (-1) per vesicle. This corresponds to a relaxivity that is amplified by a factor of approximately 10 (5) compared with Gd-DTPA.
螯合钆用作有效的磁共振（MR）造影剂的能力在很大程度上取决于钆结合的水分子与周围大量水之间的快速交换速率。由于水在脂质双层中扩散缓慢，包裹有螯合钆的脂质体尚未被广泛用作MR造影剂。为了克服这一限制，我们合成了包裹有钆（Gd）螯合物的化学稳定的多孔聚合物囊泡。这些直径为125nm的聚合物囊泡由二嵌段共聚物PEO(1300)-b-PBD(2500)（PBdEO）和磷脂1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）在水溶液中组装而成。使用化学引发剂使PBdEO交联，并用表面活性剂提取POPC，从而形成高度多孔的外膜。包裹的Gd螯合物连接到树枝状聚合物上，以防止它们通过孔隙泄漏。据估计，每个聚合物囊泡平均包裹近44000个钆。由于Gd标记的树枝状聚合物的旋转相关时间较慢以及外膜多孔，顺磁性多孔聚合物囊泡的弛豫率为每钆7.2 mM⁻¹ s⁻¹，每个囊泡为315637 mM⁻¹ s⁻¹。这对应于与钆-二乙三胺五乙酸（Gd-DTPA）相比放大了约10⁵倍的弛豫率。
