State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China.
Nanoscale. 2012 Nov 7;4(21):6768-78. doi: 10.1039/c2nr31687k. Epub 2012 Sep 26.
We report a facile approach to forming dendrimer-stabilized gold nanoparticles (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers modified by diatrizoic acid (G5.NH(2)-DTA) as stabilizers for enhanced computed tomography (CT) imaging applications. In this study, by simply mixing G5.NH(2)-DTA dendrimers with gold salt in aqueous solution at room temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a mean size of 6 nm were formed. The formed DTA-containing [(Au(0))(50)-G5.NHAc-DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs are colloid stable in aqueous solution under different pH and temperature conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry analysis, and cell morphology observation reveal that the formed Au DSNPs have good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 μM. X-ray absorption coefficient measurements show that the DTA-containing Au DSNPs have enhanced attenuation intensity, much higher than that of [(Au(0))(50)-G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice in vivo with significantly improved signal enhancement. With the two radiodense elements of Au and iodine incorporated within one particle, the formed DTA-containing Au DSNPs may be applicable for CT imaging of various biological systems with enhanced X-ray attenuation property and detection sensitivity.
我们报告了一种通过使用经二乙三胺五乙酸（DTA）修饰的端胺基第五代聚（酰胺-胺）（PAMAM）树枝状大分子（G5.NH2-DTA）作为稳定剂来形成树枝状大分子稳定的金纳米粒子（Au DSNPs）的简便方法，用于增强计算机断层扫描（CT）成像应用。在这项研究中，通过在室温下将 G5.NH2-DTA 树枝状大分子简单地与金盐混合在水溶液中，能够自发形成具有平均核尺寸为 2.5nm 的树枝状大分子包裹的金纳米粒子（Au DENPs）。随后进行乙酰化反应以中和树枝状大分子上剩余的末端胺，形成平均粒径为 6nm 的 Au DSNPs。通过不同的技术对形成的含 DTA 的 [(Au(0))(50)-G5.NHAc-DTA] DSNPs 进行了表征。我们表明，Au DSNPs 在不同 pH 值和温度条件下在水溶液中具有胶体稳定性。体外溶血试验、细胞毒性试验、流式细胞术分析和细胞形态观察表明，形成的 Au DSNPs 在高达 3.0μM 的浓度下具有良好的血液相容性，并且无细胞毒性。X 射线吸收系数测量表明，含 DTA 的 Au DSNPs 的衰减强度增强，明显高于不含 DTA 或 Omnipaque 的相同摩尔浓度的活性元素（Au 或碘）的 [(Au(0))(50)-G5.NHAc] DENPs。形成的含 DTA 的 Au DSNPs 可用于体外癌细胞的 CT 成像以及体内小鼠血池 CT 成像，信号增强明显。由于一个粒子中包含了两个放射性密度元素 Au 和碘，因此形成的含 DTA 的 Au DSNPs 可能适用于具有增强的 X 射线衰减特性和检测灵敏度的各种生物系统的 CT 成像。
