Magnetic/Upconversion Fluorescent NaGdF4:Yb,Er Nanoparticle-Based Dual-Modal Molecular Probes for Imaging Tiny Tumors in Vivo
Magnetic/Upconversion Fluorescent NaGdF4:Yb,Er Nanoparticle-Based Dual-Modal Molecular Probes for Imaging Tiny Tumors in Vivo
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基于磁性/上转换荧光 NaGdF4:Yb,Er 纳米颗粒的双模态分子探针，用于体内微小肿瘤成像
DOI：
10.1021/nn4030898
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发表时间：
2013-08-01
期刊：
影响因子：
17.1
通讯作者：
Gao, Mingyuan
中科院分区：
文献类型：
--
作者：
Liu, Chunyan;Gao, Zhenyu;Gao, Mingyuan
早期恶性肿瘤的检测在临床上仍然很困难，因此非常需要开发超灵敏的成像剂。由于f电子具有不寻常的磁性和光学性质，稀土元素非常适合用于制造可能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，可以集成稀土元素的多功能独特性能。然而，基于稀土纳米颗粒的肿瘤探针的开发仍然很困难，这不仅挑战了纳米颗粒的物理性质，而且也挑战了探针设计的合理性。在这里，我们报告了新的方法，尺寸控制合成的磁性/上转换荧光NaGdF 4：Yb，Er纳米晶体和它们的应用，在体内成像微小肿瘤。通过独立改变F-：Ln（3+）和Na+：Ln（3+）的比例，研究了尺寸和形状调节机制。通过用一端带有马来酰亚胺基团、另一端带有两个磷酸基团的PEG 2000取代油酸配体，得到了具有优化尺寸和上转换荧光的PEG化NaGdF 4：Yb，Er纳米粒子。因此，作为概念验证，通过“点击”反应将抗肿瘤抗体共价连接到PEG化的NaGdF 4：Yb，Er纳米颗粒来制备双模态分子肿瘤探针。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的研究，以成像体内腹膜内肿瘤和皮下肿瘤。由于分子探针的优异性能，小于2 mm的肿瘤成功地在体内成像：此外，对不同尺寸的颗粒进行药代动力学研究，以揭示颗粒尺寸依赖的生物分布和消除途径。
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 nanopartide-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.