Yoshida Mutsumi, Roh Kyung-Ho, Lahann Joerg
Department of Chemical Engineering, University of Michigan, 2300 Hayward Street, Ann Arbor, MI 48109, USA.
Biomaterials. 2007 May;28(15):2446-56. doi: 10.1016/j.biomaterials.2007.01.048. Epub 2007 Feb 20.
Advances in nanotechnology, in particular the development of novel types of nanoparticles, will result in advanced tools for biomedical research and clinical practice. One exciting aspect of future nanomaterial research will be the possibility to combine therapy and imaging in multifunctional nanoparticle designs. In this context, anisotropic particles with subcellular dimensions may offer so far unattainable capabilities, because they could provide access to directional information with respect to nanoparticle-cell interactions. We have recently developed an electrified jetting process, which can produce water-stable polymer particles with two distinct phases. To address the first critical hurdle towards the application of these biphasic nanocolloids as imaging probes, short-term biocompatibility was evaluated using model cell culture systems. Exposure of human endothelial cells and murine fibroblasts to biphasic nanocolloids made of 0.5% polyacrylic acid and 4.5% poly(acrylamide-co-acrylic acid) did not affect cell proliferation as determined by a colorimetric proliferation assay. Moreover, double staining with Annexin V and propidium iodide and subsequent flow cytometric analysis indicated high cell viability, although slightly decreased viability was observed at the highest dose tested (1mg particles/10(6) seeded cells). Particle internalization as well as surface binding occurred simultaneously for both cell types, as evidenced by confocal laser scanning microscopy. Taken together, these results suggest excellent short-term biocompatibility in physiological systems for wide concentration ranges of the biphasic nanocolloids and open possibilities for future work investigating receptor- or surface marker-mediated targeting.
纳米技术的进步,尤其是新型纳米颗粒的开发,将为生物医学研究和临床实践带来先进的工具。未来纳米材料研究一个令人兴奋的方面将是在多功能纳米颗粒设计中结合治疗与成像的可能性。在这种背景下,具有亚细胞尺寸的各向异性颗粒可能会提供目前尚无法实现的能力,因为它们能够提供有关纳米颗粒与细胞相互作用的方向信息。我们最近开发了一种带电喷射工艺,它可以生产具有两个不同相的水稳定聚合物颗粒。为了解决将这些双相纳米胶体用作成像探针应用过程中的第一个关键障碍,我们使用模型细胞培养系统评估了其短期生物相容性。通过比色增殖试验测定,人内皮细胞和鼠成纤维细胞暴露于由0.5%聚丙烯酸和4.5%聚(丙烯酰胺 - 共 - 丙烯酸)制成的双相纳米胶体中并不影响细胞增殖。此外,用膜联蛋白V和碘化丙啶进行双重染色并随后进行流式细胞术分析表明细胞活力很高,尽管在测试的最高剂量(1mg颗粒/10(6)个接种细胞)下观察到活力略有下降。共聚焦激光扫描显微镜证实,两种细胞类型均同时发生颗粒内化以及表面结合。综上所述,这些结果表明在生理系统中,双相纳米胶体在很宽的浓度范围内具有出色的短期生物相容性,并为未来研究受体或表面标志物介导的靶向作用开辟了可能性。