Kang Kyung Aih, Nguyen Mai-Dung
Department of Chemical Engineering, University of Louisville, Louisville, KY, USA.
Adv Exp Med Biol. 2017;977:399-407. doi: 10.1007/978-3-319-55231-6_52.
Gold nanoparticle (GNP) based contrast agents that are highly specific and sensitive for both optical and X-ray/CT imaging modalities are being developed for detecting the cancer expressing nucleolin and matrix metallo-proteinase 14 (MMP-14) on the cell membrane: Nucleolin is normally present in the nucleus. For many cancer cells, however, it is over-expressed on the cell membrane, having it to be a good cancer marker. Aptamer AS1411 is known to be an excellent target for nucleolin and also known to treat several cancer types; and MMP-14 in cancer is involved in tumor angiogenesis, blood vessel re-organization, and metastasis. In the proposed agent, AS1411 is selected as the cancer targeting molecule; and the unique property of GNPs of modulating fluorescence are utilized to allow the agent to trigger its fluorescence upon reacting with MMP-14, at an enhanced fluorescence level. GNPs are also natural X-ray/CT contrast agent. Here, as a part of on-going development of the dual-modality contrast agent, we report that conjugating a safe, NIR fluorophore Cypate at a precisely determined distance from the GNP enhanced the Cypate fluorescence up to two times. In addition, successful conjugation of the nucleolin target AS1411 onto the GNP was confirmed and among the GNPs size range 5-30 nm tested, 10 nm GNPs showed the highest X-ray/CT enhancement.
基于金纳米颗粒（GNP）的造影剂正被开发用于检测细胞膜上表达核仁素和基质金属蛋白酶14（MMP - 14）的癌症，这种造影剂对光学和X射线/CT成像模式都具有高度特异性和敏感性：核仁素通常存在于细胞核中。然而，对于许多癌细胞来说，它在细胞膜上过度表达，使其成为一种良好的癌症标志物。已知适体AS1411是核仁素的优良靶点，也已知可治疗多种癌症类型；癌症中的MMP - 14参与肿瘤血管生成、血管重组和转移。在所提出的造影剂中，AS1411被选作癌症靶向分子；利用金纳米颗粒调节荧光的独特性质，使造影剂在与MMP - 14反应时以增强的荧光水平触发其荧光。金纳米颗粒也是天然的X射线/CT造影剂。在此，作为双模态造影剂持续开发的一部分，我们报告在距金纳米颗粒精确确定的距离处缀合一种安全的近红外荧光团Cypate，可使Cypate荧光增强两倍。此外，证实了核仁素靶点AS1411成功缀合到金纳米颗粒上，在所测试的5 - 30 nm尺寸范围内的金纳米颗粒中，10 nm的金纳米颗粒显示出最高的X射线/CT增强效果。
