Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
ACS Nano. 2013 Aug 27;7(8):7227-40. doi: 10.1021/nn4030898. Epub 2013 Jul 26.
Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a "click" reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.
早期恶性肿瘤的检测在临床上仍然具有挑战性；因此，非常需要开发超灵敏的成像剂。由于 f 电子的独特磁学和光学性质，稀土元素非常适合用于创建潜在用于肿瘤成像的功能材料。纳米级颗粒提供了这样一个平台，可以整合稀土元素的多种独特性质。然而，开发适合体内微小肿瘤成像的基于稀土纳米粒子的肿瘤探针仍然具有挑战性，这不仅挑战了纳米粒子的物理性质，也挑战了探针设计的合理性。在这里，我们报告了用于控制合成磁性/上转换荧光 NaGdF4:Yb,Er 纳米晶体的尺寸的新方法及其在体内微小肿瘤成像中的应用。通过独立改变 F(-):Ln(3+)和 Na(+):Ln(3+)的比例，研究了尺寸和形状的调节机制。通过用一端带有马来酰亚胺基团和另一端带有两个磷酸基团的聚乙二醇 2000 取代油酸配体，获得了具有优化尺寸和上转换荧光的聚乙二醇化 NaGdF4:Yb,Er 纳米粒子。相应地，通过“点击”反应将抗肿瘤抗体共价连接到聚乙二醇化 NaGdF4:Yb,Er 纳米粒子上，制备了一种双模式分子肿瘤探针，作为概念验证。通过磁共振成像和上转换荧光成像对肿瘤检测进行了系统研究，以在体内对腹腔内肿瘤和皮下肿瘤进行成像。由于分子探针的优异性能，成功地在体内对小于 2 毫米的肿瘤进行了成像。此外，还进行了不同尺寸颗粒的药代动力学研究，以揭示颗粒尺寸依赖性的生物分布和消除途径。
