Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan St. (MC 063), Chicago, IL 60607, USA.
Cancers (Basel). 2010 Nov 18;2(4):1911-28. doi: 10.3390/cancers2041911.
We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates' syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy.
我们报告了两种叶酸缀合金纳米粒子(AuNP)的合成、特性和体外试验的比较研究,这两种 AuNP 在连接子和 AuNP 尺寸上有所不同,用于选择性靶向叶酸受体阳性癌细胞。选择的连接子是 4-巯基苯并噻唑(4Atp)和 6-巯基-1-己醇(MH),与纳米缀合物产品分别命名为叶酸-4Atp-AuNP 和叶酸-MH-AuNP。我们报告了叶酸受体的组织分布及其用于靶向纳米技术的内吞作用。还报告了两种纳米缀合物的合成和特性比较,包括合成的材料和方法、紫外可见吸收光谱测量、傅里叶变换红外(FTIR)测量、透射电子显微镜(TEM)图像和尺寸分布、X 射线衍射数据、元素分析和化学稳定性比较。除了纳米缀合物的分析表征外,还在 HeLa(高叶酸受体表达)和 MCF-7(低叶酸受体表达)细胞中测量了细胞致死率。纳米缀合物本身以及强脉冲光(IPL)对细胞活力没有危害。然而,在用 IPL 刺激叶酸靶向纳米缀合物后,在 HeLa 细胞中发现约 98%的细胞杀伤,在用纳米缀合物孵育四小时后在 MCF-7 细胞中仅发现约 9%的细胞杀伤。这表明叶酸靶向在选择特定细胞群体方面是有效的。考虑到进行的各种比较,我们得出结论,叶酸-4Atp-AuNP 优于叶酸-MH-AuNP,可用于癌症治疗。