Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
ACS Appl Mater Interfaces. 2012 Jul 25;4(7):3724-9. doi: 10.1021/am300817z. Epub 2012 Jun 29.
Macromolecular magnetic resonance imaging (MRI) contrast agent Gd-DTPA-HSA (DTPA, diethylene triamine pentacetate acid; HSA, human serum albumin) as a model has been successfully conjugated with trimalonic acid modified C60 for contrast enhancement at clinically used magnetic field strength. The Gd-DTPA-HSA-C60 conjugate exhibit maximal relaxivity (r1 = 86 mM(-1) s(-1) at 0.5 T, 300 K) reported so far, which is much superior to that of the control Gd-DTPA-HSA (r1 = 38 mM(-1 )s(-1)) under the same condition and comparable to the theoretical maximum (r1 = 80-120 mM(-1) s(-1), at 20 MHz and 298 K), indicating the synergistic effect of HSA and carboxylfullerene on the increased contrast enhancement. TEM characterization reveals that both Gd-DTPA-HSA-C60 and Gd-DTPA-HSA can penetrate the cells via endocytosis and trans-membrane, respectively, suggesting the potential to sensitively image the events at the cellular and subcellular levels. In addition, the fusion of fullerene with Gd-DTPA-HSA will further endow the resulting complex with photodynamic therapy (PDT) property and thus combine the modalities of therapy (PDT) and diagnostic imaging (MRI) into one entity. More importantly, the payloaded Gd-DTPA may substitute for other more stable Gd-DOTA and HSA as a theranostic package can further work as a drug delivery carrier and effectively control drug release through proteolysis.
超分子磁共振成像（MRI）造影剂 Gd-DTPA-HSA（DTPA，二乙三胺五乙酸；HSA，人血清白蛋白）作为模型，已成功地与三亚甲基膦酸修饰的 C60 偶联，以在临床使用的磁场强度下增强对比度。Gd-DTPA-HSA-C60 缀合物表现出迄今为止报道的最大弛豫率（在 0.5 T、300 K 时 r1 = 86 mM(-1) s(-1)），比相同条件下的对照 Gd-DTPA-HSA（r1 = 38 mM(-1 s(-1)))优越得多，与理论最大值（r1 = 80-120 mM(-1) s(-1)，在 20 MHz 和 298 K）相当，表明 HSA 和羧基富勒烯对增强对比度的协同作用。TEM 表征表明，Gd-DTPA-HSA-C60 和 Gd-DTPA-HSA 均可通过内吞作用和跨膜作用分别穿透细胞，表明有可能在细胞和亚细胞水平上灵敏地成像事件。此外，富勒烯与 Gd-DTPA-HSA 的融合将进一步赋予所得复合物光动力治疗（PDT）性质，从而将治疗（PDT）和诊断成像（MRI）的模式结合为一体。更重要的是，负载的 Gd-DTPA 可能替代其他更稳定的 Gd-DOTA 和 HSA，作为一种治疗诊断包，它可以进一步作为药物输送载体，并通过蛋白水解有效地控制药物释放。
