Sub-10 nm Water-Dispersible beta-NaGdF4:X% Eu3+ Nanoparticles with Enhanced Biocompatibility for in Vivo X-ray Luminescence Computed Tomography
Sub-10 nm Water-Dispersible beta-NaGdF4:X% Eu3+ Nanoparticles with Enhanced Biocompatibility for in Vivo X-ray Luminescence Computed Tomography
复制标题
亚10%20nm%20水分散%20beta-NaGdF4:X%%20Eu3+%20纳米颗粒%20with%20增强%20生物相容性%20for%20in%20Vivo%20X射线%20发光%20计算%20断层扫描
DOI：
10.1021/acsami.7b11295
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发表时间：
2017
影响因子：
9.5
通讯作者：
Lu Hongbing
中科院分区：
文献类型：
--
作者：
Zhang Wenli;Shen Yingli;Liu Miao;Gao Peng;Pu Huangsheng;Fan Li;Jiang Ruibin;Liu Zonghuai;Shi Feng;Lu Hongbing
X射线发光计算机层析成像(XLCT)作为一种新型的分子和功能成像手段，在生物医学和临床前研究中显示出巨大的应用潜力。然而，X射线激发发光材料仍然存在一些局限性，如发光效率低、生物相容性差、细胞毒性大等，这使得体内XLCT成像具有很大的挑战性。在这项研究中，我们首次提出了使用经过聚丙烯酸表面修饰的亚10 nmβ-NaGdF4：X%Eu~(3+)纳米粒子作为体内XLCT应用的发光探针，该纳米粒子具有优异的发光效率、均匀的尺寸分布、水的分散性和生物安全性。成功地合成了纯六方相(β-)NaGdF4，并用X射线粉末衍射仪和透射电子显微镜对其进行了表征，X射线光电子能谱、能谱和元素分析进一步证实了Eu3+离子的掺入。在X射线激发下，当Eu3+的掺杂量为15%时，β-NaGdF4纳米粒子的发光强度最高。值得注意的是，Eu3+的掺杂水平对NaGdF4基基质的晶相和形貌没有影响。然后对β-NaGdF_4：15%Eu~(3+)纳米粒子进行聚丙烯酸修饰，以提高水的分散性和生物相容性。通过体外细胞毒性、物理模型和体内成像实验，系统地研究了使用该纳米粒子的体内XLCT成像的兼容性。PAA修饰的纳米粒子具有超低的细胞毒性，在200μg/mL的高浓度处理下，SH-SY5Y细胞的细胞存活率超过80%，克服了体内应用的主要障碍。此外，PAA修饰的纳米颗粒的高发光强度使在体XLCT成像的定位误差小于2 mm，这与商业上可用的块体材料Y2O3：15%Eu3+的定位误差相当。所提出的纳米颗粒将XLCT研究推进到体内阶段。进一步用生物功能分子修饰这些纳米粒子可能使靶向XLCT成像成为可能。
As a novel molecular and functional imaging modality, X-ray luminescence computed tomography (XLCT) has shown its potentials in biomedical and preclinic applications. However, there are still some limitations of X-ray-excited luminescent materials, such as low luminescence efficiency, poor biocompatibility, and cytotoxicity, making in vivo XLCT imaging quite challenging. In this study, for the very first time, we present on using sub-10 nm β-NaGdF4:X% Eu3+nanoparticles with poly(acrylic acid) (PAA) surface modification, which demonstrate outstanding luminescence efficiency, uniform size distribution, water dispersity, and biosafety, as the luminescent probes for in vivo XLCT application. The pure hexagonal phase (β-) NaGdF4has been successfully synthesized and characterized by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM), and then the results of X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDX), and elemental mapping further confirm Eu3+ions doped into NaGdF4host. Under X-ray excitation, the β-NaGdF4nanoparticles with a doping level of 15% Eu3+exhibited the most efficient luminescence intensity. Notably, the doping level of Eu3+has no effect on the crystal phase and morphology of the NaGdF4-based host. Afterward, β-NaGdF4:15% Eu3+nanoparticles were modified with PAA to enhance the water dispersity and biocompatibility. The compatibility of in vivo XLCT imaging using such nanoparticles was systematically studied via in vitro cytotoxicity, physical phantom, and in vivo imaging experiments. The ultralow cytotoxicity of PAA-modified nanoparticles, which is confirmed by over 80% cell viability of SH-SY5Y cells when treated by high nanoparticle concentration of 200 μg/mL, overcome the major obstacle for in vivo application. In addition, the high luminescence intensity of PAA-modified nanoparticles enables the location error of in vivo XLCT imaging less than 2 mm, which is comparable to that using commercially available bulk material Y2O3:15% Eu3+. The proposed nanoparticles promote XLCT research into an in vivo stage. Further modification of these nanoparticles with biofunctional molecules could enable the potential of targeting XLCT imaging.