Shen Feng, Poncet-Legrand Celine, Somers Sat, Slade Andrea, Yip Christopher, Duft Andy M, Winnik Françoise M, Chang Patricia L
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Biotechnol Bioeng. 2003 Aug 5;83(3):282-92. doi: 10.1002/bit.10674.
Implanting recombinant cells encapsulated in alginate microcapsules to secrete therapeutic proteins has been proven clinically effective in treating several murine models of human diseases. However, once implanted, these microcapsules cannot be assessed without invasive surgery. We now report the preparation and characterization of a novel ferrofluid to render these microcapsules visible with magnetic resonance imaging (MRI). The ferrofluid was prepared as a colloidal iron oxide stabilized in water by alginate. The presence of iron particles in the ferrofluid was verified with chemical titration, dynamic light scattering, and magnetization measurement. The microcapsules fabricated with various concentrations of the ferrofluid in the core, or on the surface of alginate microcapsules, or both, all produced microcapsules with smooth surfaces as shown with light and scanning electron microscopy. However, at the nanoscale level, as revealed with atomic force microscopy, the ferrofluid-fabricated microcapsules demonstrated increased granularity, particularly when the ferrofluid was used to laminate the surface. From the force spectroscopy measurements, these modified microcapsules showed increasing surface rigidity in the following order: traditional alginate < ferrofluid in the core < ferrofluid on the surface. Although the mechanical stability of low-concentration ferrofluid (0.1%) microcapsules was reduced, increasing concentrations, up to 20%, were able to improve stability. When these ferrofluid microcapsules were examined with MRI, their T(2) relaxation time was reduced, thereby producing increased contrast readily detectable with MRI, whereas the traditional alginate microcapsules showed no difference when compared with water. In conclusion, such ferrofluid-enhanced alginate is suitable for fabricating microcapsules that offer the potential for in vivo tracking of implanted microcapsules without invasive surgery.
将包裹在藻酸盐微胶囊中的重组细胞植入以分泌治疗性蛋白质,已在治疗几种人类疾病的小鼠模型中被证明具有临床疗效。然而,一旦植入,这些微胶囊在不进行侵入性手术的情况下就无法进行评估。我们现在报告一种新型铁磁流体的制备和表征,以使这些微胶囊能够通过磁共振成像(MRI)可见。该铁磁流体是通过藻酸盐在水中稳定的胶体氧化铁制备而成。通过化学滴定、动态光散射和磁化测量验证了铁磁流体中铁颗粒的存在。在藻酸盐微胶囊的核心、表面或两者中加入不同浓度铁磁流体制造的微胶囊,用光镜和扫描电子显微镜观察均显示表面光滑。然而,原子力显微镜显示,在纳米尺度上,用铁磁流体制造的微胶囊粒度增加,特别是当铁磁流体用于包裹表面时。从力谱测量结果来看,这些修饰后的微胶囊表面刚性按以下顺序增加:传统藻酸盐微胶囊<核心含有铁磁流体的微胶囊<表面含有铁磁流体的微胶囊。虽然低浓度(0.1%)铁磁流体微胶囊的机械稳定性降低,但浓度增加至20%时能够提高稳定性。当用MRI检查这些铁磁流体微胶囊时,其T(2)弛豫时间缩短,从而在MRI上产生易于检测到的增强对比度,而传统藻酸盐微胶囊与水相比则无差异。总之,这种铁磁流体增强的藻酸盐适用于制造微胶囊,为在不进行侵入性手术的情况下对植入微胶囊进行体内追踪提供了可能。